In order to elucidate a possible role of hydro-dynamics in atherogenesis, we have studied (i) the vessel geometries and (ii) the flow disturbances in the coronary artery bifurcations of the pig.
Intact fresh hearts, each of which included the ascending aorta, were obtained at a local slaughterhouse. The molds of some coronary arterial systems were constructed by using a plastic resin, Technovit 4143-C (Kulzer & Co. G. m. b. H.), to investigate in detail the architecture of the heart vessels. The left coronary artery (LCA), after arising from the sinus of the aorta, runs a short distance in the form of the funnel-shaped convergence and gives off the left circumflex (LCX) and anterior descending (LAD) arteries. The LCX and its branches were characterized by Y-shaped bifurcations. On the other hand, the LAD and their tributaries showed distinctive features of side branches. The same features are also observed in the right coronary artery (RCA) and its branches. As the main stem of the RCA branches off the rami atrioventriculares, it curves sharply. In the case of the Y-shaped bifurcation, the parent vessel changes its cross section from a circle to a dumbbell via an ellipse when it bifurcates. The elastic hoop stress acting the wall due to a pressure load is not uniform in tubes with such a non-symmetric cross section. Therefore stress or strain concentration may be expected at the bifurcations and this kind of non-uniformity might be a factor in atherogenesis.
To visualize the flow pattern in the coronary artery bifurcations, the major coronary arteries with the ascending aorta were made transparent after removing the surrounding myocardial tissues. The test fluid was used to perfuse the transparent vessels at a constant flow rate in the physiological range. Secondary flow, which has a similar pattern to the horseshoe vortex produced around a wall-based protuberance in a tube, was generated at the bifurcations except for the first LCA branching site. The lack of secondary flow at the LCA bifurcation is attributable to the appreciable decrease in total cross-sectional area after the bifurcation. This area reduction is typical in pig heart vessels but not in humans. Therefore we can expect the generation of secondary flow at the human LCA bifurcation. The secondary flow produces complicated flow field around the bifurcations in collaboration with flow separation, which is occasionally generated due to the flow division ratio between the branches and geometrical abnormalities. The disturbed flow affects wall shear stress distribution and movements of particulate elements of blood, which may lead the disease process of atherosclerosis.

View full abstract

Quiescent smooth muscle cells (SMC) obtained from atherosclerotic intima of rabbit (intimal SMC) received an atherogenic diet showed different proliferative activity from medial SMC of normal rabbit aorta (medial SMC). Intimal SMC kept high proliferative capacity (saturation density: 6.35±1.83×10⁴ cells/cm²) until at least 30th passage, though normal medial SMC showed lower saturation density (1.12±0.47×10⁴ cells/cm²) and lost growth ability after 4th passage. After an initial lag phase, DNA synthesis of medial SMC in medium containing normal rabbit serum increased rapidly with a maximum after 26 hours. Stimulation with medium containing hyperlipidemic serum did not change the kinetics of DNA synthesis. DNA synthesis of intimal SMC in medium with either normal or hyperlipidemic serum reached maximum rate between 26 and 30 hours after medium change. DNA synthesis of medial SMC stimulated, twice with an interval, by hyperlipidemic serum for 8 or 24 hours was significantly higher than in the control. On the stimulation by hyperlipidemic serum, intimal SMC reacted in a similar fashion to medial SMC. In both medium containing either hyperlipidemic or normal serum, ³H-thymidine uptake of intimal SMC was higher than medial cells. Hyperlipidemic serum did not stimulate further DNA synthesis of both medial and intimal SMC in logarithmic growth phase.
It appeared that enhancement of DNA synthesis by an exposure to hyperlipidemic serum in both medial and intimal SMC did not depend upon the changes of intracellular lipid content during incubation times. However the ratio of phospholipid to free cholesterol seemed to be correlate to the increasing of DNA synthesis.
Insulin in 1 or 5μg/ml concentration stimulated to proliferation of both medial and intimal SMC. However the stimulatory response of intimal SMC was lower than that of medial SMC.
Intimal SMC had more resistibility to the cytotoxic effect of hyperlipidemic serum, measured by the ⁵¹Cr-release from cell membrane than medial SMC. It is possible that intimal smooth muscle cells can proliferate intensely without stimulation by specific growth factor and making resistance to the cytotoxic effect of hyperlipidemic serum and induce atherosclerosis.

View full abstract

Since the discoveries of platelet-derived growth factor and thromboxane A₂, there have been growing interests in the involvement of platelets in the pathogenesis of atherosclerosis. Little is known, however, about the roles of platelets in the vascular injury initiating atherosclerosis. We have performed both in vivo and in vitro studies on this critical issue.
1) In vivo study
Fifteen healthy male rabbits were used. A No. 4F Swan-Ganz catheter was inserted into the right carotid artery of the rabbit to the orifice of the aorta, where serotonin 100μg/kg, TXA₂ (PGH₂ 25μg+platelet microsome 4mg), STA₂ (1μg/kg) or platelets (6×10⁸) activated by collagen were flushed just after the balloon was inflated to temporarily obstruct the forward blood flow. Histological exam showed varying degrees of edematous changes in the intima and media of the coronary artery and aorta. Activated platelets produced most striking changes, followed by TXA₂, STA₂ and serotonin.
2) In vitro study
Confluent vascular endothelial and smooth muscle cells grown in culture dish were used. Addition of activated platelets to the media resulted in damage to the cultured cells dose- and time-dependently as estimated by [³H]adenine release. Methysergide 10^-6M, a serotonin antagonist or ONO 3708 10^-5M, a thromboxane A₂ antagonist only partially prevented these changes, while ZK 36374 10^-6M, a prostacyclin analogue or IBMX 10^-3M, a phosphodiesterase inhibitor potently inhibit the increase of [³H]adenine release. Although TXA₂, STA₂ and serotonin caused dose-dependent damage to the cells, PDGF had no effects, up to the concentration of 200ng/ml.
We conclude that activated platelets may initiate atherosclerotic changes by injuring the vascular wall and that agents which elevate cyclic AMP levels may prevent the damage induced by these platelets.

View full abstract

The effect of pantethine on plasma β-thromboglobulin and lipid and lipoprotein levels was studied in diabetics. Sixteen patients in whom plasma β-thromboglobulin levels were raised (>50ng/ml) received pantethine with a dose 600mg/day for the first three months and 1, 200mg/day for the next six months. Plasma β-thromboglobulin levels decreased significantly after 9 months of administration of pantethine, compared to pretreatment level. Plasma triglyceride, apo E and apo C-II levels decreased significantly after 9 months of administration of pantethine. Plasma total cholesterol levels decreased significantly after 3 and 9 months of treatment. Plasma LDL-C and apo B levels tended to decrease after treatment. It is concluded that pantethine is an effective plasma β-thromboglobulin-lowering drug as well as a lipid-lowering drug.

View full abstract

The effects of niceritrol on serum lipids and apolipoproteins were investigated in 29 patients with hyperlipidemia for 12 weeks. Total cholesterol was decreased significantly by 5.4% after the treatment without lowering HDL cholesterol. The atherogenic index was decreased significantly. Serum triglyceride had a tendency to decrease but not significantly. In 13 patients with hypertrigly-ceridemia (more than 150mg/dl of triglyceride), serum triglyceride was decreased by 20%. The apolipoproteins A-I, A-II and B were decreased significantly. There were no effects on apolipoprotein C-II and C-III. Apolipoprotein E decreased significantly. Flushing occurred in 5 patients with hyperlipidemia, but other major side effects did not occure. These results suggested that niceritrol was effective in treatment of patients with hyperlipidemia.

View full abstract

Probucol reduces serum cholesterol level effectively even in patients with familial hypercholesterolemia. The long-term use of probucol enabled to show the regression of achilles tendon xanthoma and the first prevention of ischemic heart diseases. However, the mechanism of action lowering serum cholesterol is still obscure, and probucol also reduce HDL-cholesterol which has been believed to be a preventing factor against atherosclerosis. The aim of present study is to investigate the role of the liver in decreasing serum HDL-cholesterol during probucol administration. Probucol reduced VLDL-, LDL-, HDL₂ cholesterol and apoprotein A-I in both of HDL subfractions. When human apo B, E deficient HDL₃was iodinized and injected into portal vein, probucol accelerated the hepatic uptake of ¹²⁵I-HDL₂ in isolated perfused rat liver system and also in vivo. In vivo, its uptake of adrenal glands also increased significantly. Hepatic cholesterol concentration in treated rats showed slight increase in comparison to non-treated rats. We concluded that the increased uptake of HDL is one of causes of lowered serum HDL.

View full abstract

[Purpose] The effects of frequently used Clinofibrate (Lipoclin) and probucol (Sinlestal) on hyperlipidemia accompanying diabetes were evaluated. [Methods] As a joint study by 46 investigators in 46 national hospitals, Lipoclin was administered at a daily dose of 600mg to 148 males and 267 females with diabetes mellitus (DM), and total HDL cholesterol (HDL-C), triglycerides (TG), the arteriosclerosis index (A. I.), and HbA₁C were studied. In addition, Sinlestal was administered to 78 patients with hyperlipidemia persisting after blood sugar was controlled (18 males, mean age 50.5 years; 60 females mean age 61.5 years) and its effects were compared with those of the Lipoclin group. The effects of combined administration of Sinlestal, Pantethine (600mg), and Trapidil in preventing a decrease in HDL-C caused by Sinlestal were also evaluated in 50 of these patients with intractable hyperlipidemia. [Results] Lipoclin significantly reduced TC, TG, and HbA₁C but increased HDL-C. Sinlestal markedly reduced TC even in patients who did not respond to Lipoclin, but significantly reduced HDL-C. The combined administration with Pantethine and Trapidil, inhibited the decrease in HDL-C, especially markedly when the dose of Sinlestal was reduced.

View full abstract

Melinamide (N-α-methylbenzyl linoleamide) is known to inhibit hydrolysis of cholesterol ester in intestinal lumen. We studied the effect of melinamide on plasma lipids and lipoproteins of human subjects with dietary cholesterol (chol) loading (6 eggs; 1, 650mg of chol/day). The design was a cross-over trial in which 2 subjects received dietary chol loading for 3 weeks following with ordinary Japanese foods (chol 450mg/day) for 6 weeks. Then same subjects received chol loading with melinamide (2, 250mg/day) for next 3 weeks. Two other subjects received chol loading with melinamide for first 3 weeks, then ordinal Japanese foods for next 6 weeks and chol loading without melinamide for final 3 weeks. Plasma chol and high-density lipoprotein chol (HDL-chol) were determined before and after chol loading with or without melinamide. Mean plasma chol and HDL-chol were increased slightly on chol loading (193±18 to 208±23mg/dl; 58±15 to 64±16mg/dl). But additional melinamide on chol loading did not change plasma chol even though increased HDL-chol significantly (196±4 to 194±7mg/dl; 56±12 to 64±12mg/dl). We also determined plasma chol distribution among lipoproteins separated by agarose column chromatography. Chol loading produced additional lipoprotein chol peak between very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) which appeared to be so-called small VLDL. However additional melinamide could inhibit appearance of small VLDL chol peak. These data suggested that melinamide seemed to be a drug of choice for treatment of hyperlipidemic subjects being affected by dietary cholesterol.

View full abstract

The effect of Melinamide [N-(α-Methylbenzyl) linoleamide], a cholesterol absorption inhibitory agent, on lipid metabolism for hypercholesterolemic diabetic patients were investigated.
Thirty three diabetic subjects whose plasma cholesterol greater than 250mg/dl were given 1, 500mg/day of Melinamide per orally for six months. Plasma cholesterol (ch), triglyceride (TG), HDL, HDL₂ and HDL₃-ch, LDL-ch and Apoprotein (Apo) A-I, A-II concentrations were determined every two months during study.
Though plasma TG showed no remarkable change, plasma and LDL-ch fell by 15% and 17 (p<0.05). HDL-ch also decreased significantly (p<0.05) mainly due to lowering of HDL₂-ch. Plasma Apo A-I level did not change but Apo A-II decreased significantly during study indicating relative Apo A-I enrichment of HDL.
These results indicated that Melinamide is a potent agent for lowering plasma cholesterol in hypercholesterolemic diabetic subjects. Whether HDL decrement associated with compositional change affect the development of atherosclerosis must be explored further.

View full abstract

The effect of Melinamide on the serum lipid and apolipoprotein was studied in the subjects with hypercholesterolemia. The significant decrease of serum cholesterol and phospholipid, and concomitant increase of HDL₂/HDL₃ ratio (p<0.05) were observed after Melinamide administration (2, 250mg/day, 16 weeks). The tendency of decrease in the levels of apo A-IV and B was demonstrated especially in the cases whose cholesterol reduced during therapy. These results suggested the serum apo A-IV might reflect the decrease of the exogenous cholesterol after Melinamide therapy.

View full abstract

The present study was undertaken to elucidate the effect of combined therapy with clinofibrate and melinamide on serum lipid. Thirteen patients with type ha hyperlipidemia were divided into two groups. Six patients were given clinofibrate and seven patients were given melinamide for first 12 weeks. And then all patients were given both clinofibrate and melinamide for additional 24 weeks. Blood samples were collected at 12 hours fasting in order to measure cholesterol (ch.) and triglyceride (TG) in whole serum and lipoprotein fractions (VLDL, LDL, HDL, HDL₂ and HDL₃) and apolipoprotein (A-I, A-II, B, C-II, C-III and E) before therapy and at every 12 weeks.
The results obtained were as follows:
(1) Only total ch. decreased significantly with single therapy of both clinofibrate and melinamide. With combined therapy the significant decrease in VLDL ch., LDL ch. and total TG level were recognized. HDL ch. also decreased significantly associated with HDL₂ ch. subfraction level.
(2) In apolipoprotein profile, clinofibrate decreased apo A-I and melinamide increased apo E significantly with each single therapy, respectively. Apo A-I, A-II and C-III decreased significantly with combined therapy.
(3) Atherogenic index (HDL ch./LDL ch. ratio) did not change in all period, but the differences between LDL ch. and HDL ch. (LDL ch.—HDL ch.) was decreased significantly with combined therapy. We concluded that combined therapy decreased not only the atherogenic lipoproteins, but also the antiatherogenic lipoproteins. So further investigation is necessary to clarify whether combined therapy is effective on hyperlipidemia and atherogenic index is an adequate parameter on purpose to evaluate antihyperlipidemic drug effect.

View full abstract

By the criteria of 75g OGTT, glucose intolerances such as diabetic type and borderline type were determined in cases aged 30 to 70 years.
1) The decrements of FBS during the periods of 4 months were accompanied by the decrements of serum cholesterol or triglyceride levels in 68 male cases with diabetes mellitus.
2) There were no correlations between FBS and serum cholesterol, triglyceride, HDL cholesterol, HDL-C/Chol, apoproteins A-I, A-II or B, nutritional intakes or fat energy ratio in 63 male or female cases with glucose intolerance. But there was a negative correlation between FBS and protein energy ratio. On the other hand there was a positive correlation (r=0.88) between HbA₁c and FBS measured one month before. There was a positive correlation between HbA₁c and carbohydrate energy ratio, while a negative one between HbA₁c and A-I or protein energy ratio. Therefore it is desirable for improving blood sugar control to decrease carbohydrate energy ratio and to increase protein energy ratio.
3) There were positive correlations between relative body weight ratio and serum cholesterol or triglyceride, between the rate of body weight changes and FBS, and between the rate of body weight changes and ingested energy or carbohydrate volumes to the prescribed ones in 110 male or female cases with glucose intolerance. There was also a positive correlation between the rate of body weight changes and carbohydrate energy ratio, while a negative one between that and protein energy ratio. Therefore it is desirable for the decrement of body weight to decrease the intakes of energy or carbohydrate and to increase protein energy ratio.
4) More than 80 kcal of alcohol per day resulted in poor blood sugar control in 50 male cases with glucose intolerance. Serum triglyceride or _γGTP levels tended to increase by drinking alcohol beverages everyday in obese cases with glucose intolerance.

View full abstract

Pantethine and probucol are known to lower serum low density lipoprotein-cholesterol (LDL-C). Pantethine is reported to elevate high density lipoprotein-cholesterol (HDL-C). But probucol lowers HDL-C. The clinical significance of latter effect is still controversial. To evaluate whether combination of both agents prevent the lowered HDL-C by probucol, the effects of each agents alone and combinational effects on cholesterol metabolism in primary cultured hepatocytes were compared. Primary cultured hepatocytes were prepared from rabbit liver by collagenase treatments, and cultured in 10% FCS-DME medium containing 10^-7M insulin. LDL and HDL were prepared by ultracentrifugation from human serum. VLDL-cholesterol synthesis from [¹⁴C] acetate were analyzed with thin layer chromatography. For uptake study, LDL-[¹⁴C]cholesterol linoleate and HDL-[¹⁴C]cholesterol linoleate were incubated with hepatocytes for 8hrs. Secretion of bile acids was analyzed with degradative radioactivity form [³H]cholesterol, LDL or HDL-[¹⁴C] cholesterol linoleate. Both pantethine and probucol decreased synthesis of VLDL-lipid from [¹⁴C] acetate. Both agents increased LDL-C uptake into hepatocytes. Pantethine decreased incorporation of HDL-C, but probucol increased incorporation of HDL-C. These results were consistent with the serum lipoprotein changes observed in clinical studies. Combinational addition of pantethine and probucol to cultured hepatocyte decreased VLDL-C synthesis from acetate additively, and increased LDL-C incorporation, but decreased HDL-C incorporation. These results obtained from hepatocytes suggests that combination therapy may prevent HDL-C lowering effect of probucol.

View full abstract

In order to evaluate usefulness of plasma apolipoprotein determination in prediction of the presence and severity of coronary atherosclerosis, plasma concentrations of lipids, lipoproteins and apolipoproteins (apo) were measured in 56 male patients whose coronary atherosclerosis were assessed by coronary angiography. The subjects were 56 male patients, aged 42-74 years old, who were referred to Fukui Medical School Hospital for coronary angiographic evaluation of coronary artery disease (CAD) because of chest pain. Age of the 48 patients (86%) was over 50 years old. Coronary cine angiography was carried out by the selective technique of Sones. The presence of coronary atherosclerosis was defined as 75% or greater narrowing of luminal diameter. Thirty-eight (68%) of 56 patients were classified as CAD group. Single vessel and multivessel CAD group consisted of 23 (41%) and 15 (27%) patients, respectively. Eighteen patients (32%) exhibited normal coronary artery (NCA group).
The following results were obtained:
1. The risk factors for coronary atherosclerosis such as age, smoking and blood pressure were matched among NCA group, single vessel CAD group and multivessel CAD group.
2. There were no significant differences in plasma concentrations of lipids (total cholesterol and triglyceride), LDL-cholesterol and HDL-cholesterol among three groups.
3. Plasma levels of apo A-I and apo B and the ratio of apo A-I/apo B correlated significantly to the presence but not to the severity of coronary atherosclerosis.
Our findings indicate that apolipoproteins are much better discriminator than lipids for coronary atherosclerosis in elderly Japanese males.

View full abstract

The present study was conducted to investigate plasma apo B rich lipoprotein responses to oral fat load with reference to the kinds of fat. Eleven healthy volunteers were subjected to receive either 40g of margarine or the same amount of butter.
After margarine load, LDL-C and LDL-TG levels dropped significantly and plasma apo B, LDL-apo B levels decreased.
On the other hand, T-C and LDL-C levels in-creased, and LDL-TG/LDL-apo B levels elevated significantly after 4 and 6 hours after butter load.
Plasma TG rose higher levels and remained elevated in the subjects with relatively high apo B. But this was not confirmed after margarine load. These results suggest that, even in the acute fat load, plasma apo B rich lipoprotein can be affected differently depending upon the kinds of fat.

View full abstract

In recent years, there has been a growing interest in the dietary factors concerned with atherosclerosis and thrombosis. Particularly, attention has focused on the polyunsaturated fatty acids (PUPA) in blood. On the other hand, apolipoproteins are considered to play an important role in the metabolism of lipoproteins. It was, therefore, important to investigate the relationship between PUFA and apolipoproteins regarding the aspects of prevention of atherosclerosis and thrombosis.
The inhabitants in Hachijoh Island (Tokyo), among whom the incidence of cerebral thrombosis is low, eat mainly fish. Here, we report the relationship between PUFA and apolipoproteins under the various TG levels studied on Hachijoh Island.
The test group was divided into three groups according to the TG level; high TG, middle TG and low TG. The ratio, eicosapentaenoic acid/arachidonic acid (EPA/AA), was significantly higher in the high TG group than the low TG group. Though EPA/AA ratio was higher in the high TG group when compared to the middle TG group, this difference was not statistically significant. In contrast, Apo A-I/Apo B ratio was significantly lower in the high TG group relative to the middle TG group and low TG group. These results showed that Apo A-I/Apo B ratio was affected by the TG level while EPA/AA ratio relatively unaffected.
In conclusion, these findings suggest that when taking fish as the preventional factor of athero-sclerosis and thrombosis, attention should be drawn not only to increase EPA/AA ratio for the inhibition of platelet aggregation but also to maiptaro the TG level correctly.

View full abstract

Coronary arterial lesions were studied in 54 six-month-old swine which were fed rations supplemented with 20% margarine, 20% hydrogenated coating fat or 20% butter fat. The plasma cholesterol levels increased over control animals in the hydrogenated coating fat and butter fat groups. The margarine and hydrogenated coating fat and butter fat groups had more intimal thickening with degenerate endothelial and smooth muscle cells than the basal group. The addition of 20% butter fat to the ration produced the greatest degree of intimal thickening among all experimental groups. A variety of cell types, including macrophages, neutrophiles, mast cells and smooth muscle cells, were involved in the development of lipid-rich coronary arterial lesions.

View full abstract

Species difference of lipid metabolism to estrogen treatment was studied in rabbits, rats, and chickens. Estradiol was administered to animals via subcutaneous injection or oral feeding at the doses of 2.0 or 30mg per kg body weight 8 times for two weeks. Marked and moderate increase were observed in the levels of plasma triglycerides and cholesterol respectively in chickens. While estradiol treatment resulted in decrease of plasma triglycerides and cholesterol levels in both rabbits and rats.
The ultrastructure of hepatocytes displayed lipid vacuoles, well developed endoplasmic reticulum and Golgi apparatus indicating active lipid synthesis in the liver of chickens, but not in those of rabbits and rats.

View full abstract

The present study was designed to investigate the effects of cyclobranol α-methyl ferulic acid ester (CB-MFE) on serum lipids and atherosclerosis in cholesterol-fed rabbits. CB-MFE is a derivative of phytosterol ferulic acid ester in ricegerm. White Japanese male rabbits weighing 2-3kg were fed a 1% cholesterol diet for 2 weeks, and then divided into two groups so as not to make a statistical difference in the serum total cholesterol levels between two groups. One group (n=8) was continued on a 1% cholesterol diet as control. The other group (n=9) was fed a 1% cholesterol diet plus 0.1% CB-MFE. At the end of the 14 week period, rabbits were killed and autopsied.
Result 1 The effects on serum lipids.
(1) CB-MFE lowered serum total cholesterol and phospholipid levels significantly.
(2) Although CB-MFE lowered serum lipid peroxide levels, there were no significant.
Result 2 The effects on atherosclerosis of aorta.
Sudan IV stainable aortic lesions covered 34.9±17.6% on the intimal surface in the control rabbits, and 22.9±11.6% in the CB-MFE treated rabbits. CB-MFE tended to reduce the atherosclerotic intimal involvements.
Conclusion
From a point of view of the present results and the great individual difference in rabbits, it is considered that CB-MFE has the powerfully hypocholesterolaemic and antiatherogenic activities.

View full abstract

Male and female golden hamsters were fed lithogenic glucose diets with or without 0.3 sitosterol in an attempt to investigate the effect of sitosterol on metabolism of endogenous cholesterol.
1) Plasma and hepatic total cholesterol levels were decreased and fecal total cholesterol level was increased significantly by the administration of 0.3% sitosterol.
2) The administration of 0.3% sitosterol increased biliary cholesterol significantly in female hamsters. Biliary bile acid compositions changed in both sexes.

View full abstract

The present study was undertaken to investigate the effects of atherosclerotic progression on the responsiveness of rabbit aortae to ergonovine. For this purpose, we examined the contractile responses of isolated aortae from control rabbits (n=10) and Watanabe heritable hyperlipidemic rabbits (WHHL; n=16). WHHL rabbits were divided into three groups by their age: group I is composed of rabbits younger than 10 months, group II is from 10 to 22 months and group III is older than 22 months. Macroscopic and microscopic examination of aortae obtained from WHHL-I, II and III revealed that atherosclerotic changes were slight, moderate and severe, respectively. Aortae from control rabbits had no atheromatous lesions. Those helical strips were mounted in tissue baths filled with oxygenated Krebs solution for isometric tension recording.
The concentration-response curves for phenylephrine (10^-8-3×10^-5 M) in control and WHHL-II and III groups were almost identical with similar maximum contractions. The contractile responses to ergonovine in WHHL-I were almost the same as those in controls, while the concentrationresponse curve for ergonovine (10^-10-3×10^-5M) in WHHL-II was markedly shifted to the left with significantly low threshold concentration and ED₅₀ value as compared with controls. The maximum contraction in WHHL-II was also increased. On the other hand, that for ergonovine in WHHL-III was similar to controls without any changes of ED₅₀ values and maximum contractions. Only threshold concentration to ergonovine in WHHL-III was significantly lower than that in controls.
These findings suggest that the contractile responses of rabbit aortae to α₁-adrenergic stimulation were not affected by the presence of atherosclerosis and by its progression, but those to ergonovine were affected. The contractile responses of aortae with slight atheromatous lesions were not changed as compared with controls, but aortae with moderate atherosclerosis were remarkably hyperreactive to ergonovine. In aortae with severe atherosclerosis, on the other hand, the hyperreactivity to ergonovine was markedly attenuated as compared with those with moderate atherosclerosis.

View full abstract

There is no clear rule about the progression of atherosclerosis. But, it is well known that the increase in serum lipids, especially cholesterol relates with atherosclerosis.
In present study, the content of lipids, fatty acid composition and phospholipid fraction in human aorta of adult and elderly were determined in order to examine the relationships between lipids and the progression of atherosclerosis.
Human aorta obtained at autopsy was frozen by liquid CO₂ and sectioned into intima, intimal media and media by cryostat. The each section was homogenized and the lipids were extracted with chloroform-methanol mixture and analyzed using thin-layer chromatography and gas-liquid chromatography.
In atherosclerotic lesion of adult, the contents of lipid were larger than in intact aorta. But compared with atherosclerotic lesion of elderly its progress was slow, and the rate of lipid increase, especially cholesterol was little.
In intact human aorta of elderly, especially in intima the contents of lipid were larger than in intact aorta of adult.
Compared with intact human aorta of adult, in intact of elderly and atherosclertic lesion of adult, the proportion of polyunsaturated fatty acid in phospholipid decreased, and lysolecithin increased in phospholipid fractions.
In fatty acid composition of cholesterolester, linoleic acid increased and oleic acid decreased in proportion to the distance from luminal surface. This tendency was remarkable with aging or progression of atherosclerosis.
From above findings, it was suggested that the balance between cholesterol and phospholipid, and the changes of polyunsaturated fatty acid in arterial wall played important rule in the progression of atherosclerosis.

View full abstract

Effects of lipid peroxides on antithrombin III (AT-III) and protein C in plasma were observed. Cumene hydroperoxide, tetraethoxypropane, arachidonic acid peroxide and linoleic acid hydroperoxide were used as lipid peroxides for experimental reagents. The chromogenic substrates were used for the measurements of AT-III and protein C. Following results were obtained.
1) Cumene hydroperoxide and tetraethoxypropane even in low dose reduced AT-III activity.
2) Arachidonic acid peroxide only in relative high dose reduced AT-III activity.
3) Linoleic acid hydroperoxide didn't reduce AT-III activity.
4) Cumene hydroperoxide, tetraethoxypropane and arachidonic acid peroxide didn't reduce protein C activity in same dose although they reduced AT-III activity.

View full abstract

Serum concentration and activity of Antithrombin-III, Plasminogen, α2-Plasmin inhibitor and Protein-C were measured in the patients of long term Elementary Diet Treatment.
The results obtained were as follows.
1) The serum levels of fibrinogen in patients group were significantly higher than control group. (462.43±178.59mg/dl (Pt), 255.50±32.30mg/dl (Cont), p<0.001.)
2) The serum levels of AT-III, PLg and PC were significantly lower in the patients group than control group. [AT-III: 26.84±7.90mg/dl (Pt), 32.80±3.60mg/dl (Cont). PLg: 9.44±2.96mg/dl (Pt), 17.60±2.00mg/dl (Cont), PC: 68.64±21.46% (Pt), 96.40±15.30% (Cont), p<0.05, p<0.001, p<0.001.]
3) There was no significant difference in the levels of α2-PI between patients group and control group. [4.84±1.80mg/dl (Pt), 5.01±1.22mg/ dl (Cont), N. S.]
4) The levels of activity of AT-III, PLg and α2-PI in the patients group were significantly lower than those of control group. [AT-Ill: 73.99±16.58% (Pt), 104.80±10.4% (Cont), PLg: 82.09±15.80% (Pt), 91.50±14.40% (Cont), α2-PI: 84.70±17.47% (Pt), 102.30±7.70% (Cont), p<0.001, p<0.1, p<0.01.]
These results suggested that the patients under longterm Elementary Diet Treatment were in the hypercoagulability states.

View full abstract

Carboxyl esterase can hydrolyze triolein in the presence of triolein hydrolysis promoting factor (THPF) in serum. The composition of THPF and its mechanism were investigated. THPF contained phospholipids, phosphatidyl choline, sphingomyelin and cardiolipin. Among various treatment, phopholipase C treatment lost the THPF activity. Addition of phospholipid enhanced the triolein hydrolyzing activity (Cardiolipin>phosphatidyl serine>phosphatidyl inositol, phosphatidyl choline.) But cardiolipin decreased tributyrin hydrolysis. In the presence of cardiolipin, 1M NaCl, triton X-100, mercaptoethanol ruined triolein hydrolysis, but not tributyrin. These results might consistent with the idea that cardiolipin interacted with enzyme by its negative charge in polar head group and modify the substrate specificity so as to increase the affinity for hydrophobic substrate triolein. And then, the enzyme shows triolein hydrolyzing activity.

View full abstract

The effect of stimulation of phospholipase with phorbol 12-myristate 13-acetate and lipopolysaccharide on 1-acylglycerophospholipid acyltransferase was studied in cultured rabbit aorta smooth muscle cells. The acyltransferase in smooth muscle cells without stimulation was active on a wide range of unsaturated fatty acids and was not arachidonic acid specific. On increase in phospholipase activity, acyltransferase activity only with arachidonic acid as substrate increased time-dependently. Acyltransferase activities were most increased by increasing phospholipase activities when lysophosphatidylcholine was used as acceptor. These results suggested that arachidonic acid specific acyltransferase is induced in smooth muscle cells by increase in phospholipase activities. The role of this enzyme is speculated to be the specific incorporation of endogenously released arachidonic acid.

View full abstract

In uremics, hypertriglyceridemia is common. The cause is mainly due to an impairement of the removal of triglycerides (TG) by lipoprotein lipase (LPL) reaction.
Thus, the present study was undertaken to clarify the inhibitors from uremic serum for LPL activity, in vitro.
Serum from both uremics (hemodialysis patients: HD) and normal controls (C) was obtained from venous blood and isolated by ultracentrifugation at d. 1.21g/ml to separate into lipoproteins (Lp) and Lp deficient serum (LPDS).
The LPDS was extensively dialyzed against 0.15M NaCl, 1mM EDTA, pH 7.4 and concentrated by lyophilization. The concentrated LPDS was in part further fractionated into subfractions by Sephacryl S-200 column chromatography.
LPL was purified from postheparin plasma of 50ml using Heparin-Sepharose Affinity Chromatography.
LPL assay system was consist of 1.5mM triolein, 0.02% Triton X-100, 0.1M Tris-HCl, pH 8.0, apolipoprotein (apo) C-II of 2.5μg, LPL of 10μl and inhibitors, and the total volume was 80μl. The LPL activity was determined by the method of Hernell et al.
LPL activity was depressed by increasing amounts of serum added in the assay system in both C and HD, especially in HD.
On the other hand, only extremely concentrated LPDS, about 10-fold, inhibited LPL activity and the inhibition was significantly higher in HD than in C.
However, subfractions of LPDS such as 7S and 4S showed a similar inhibitory effect on LPL activity between C and HD, even though the highly concentrated samples of 7S fractions were used.
The results in the present study suggest that there are at least 2 inhibitors in serum in both C and HD, and one is dialyzable and another is not dialyzable.

View full abstract

The role of lipoprotein lipase (LPL) in fibrinolysis was assessed using both a chromogenic substrate (S-2251, H-D-Val-Leu-Lys-pNA) specific to plasmin and a radioactive fibrinolytic assay. LPL was purified from skimmed bovine milk by affinity chromatography on heparin-Sepharose. LPL alone did not act on S-2251 but enhanced plasmin activity on it. The mixture of plasminogen, urokinase and LPL hydrolyzed S-2251 to a greater extent than the mixture of plasminogen and urokinase did. Heat treated LPL did not enhance this reaction, however, reduction of carboxymethylated LPL did, which was confirmed by a radioactive fibrinolytic assay. LPL was cleaved into several smaller proteins by plasmin as revealed by SDS-polyacrylamide gel electrophoresis, however, triolein hydrolytic activity was not affected. Since LPL is found in vascular endothelium, our data may suggest an important role of LPL in modulating fibrin clearance.

View full abstract

Aggregation and secretion of washed platelets from stroke-prone spontaneously hypertensive rats (SHRSP) were greatly reduced by the development of the hypertension compared with those of platelets from age-matched normotensive Wistar-Kyoto rats (WKY). Concomitantly, thrombin-induced phosphorylation of the 47kDa protein in SHRSP platelets was significantly decreased. However, TPA-induced aggregation, secretion and 47kDa protein phosphorylation in SHRSP platelets were similar to those in WKY platelets. Thus, it was suggested that protein kinase C activity and its substrate are normally present in SHRSP platelets, and defects are in the receptor-mediated activation of protein kinase C (Umegaki et al. FEBS 196, 139, 1986). Since diacylglycerols (DG) and Ca²⁺ reportedly play important roles in 47kDa protein phosphorylation in human platelets, the mass content of phosphatidylinositol (PI) and thrombin-induced DG formation were investigated in 12-16 weeks old SHRSP platelets in comparison with age-matched WKY platelets.
Phospholipids were extracted from platelets by CHCI₃: CH₃OH (1:2) and resolved by HPTLC using CHCI₃: McOH: CH₃NH₂ (63:35:10). Each phospholipid was determined either by fluoro-metrically or by phosphorus assay. The content of PI in SHRSP platelets was approximately 10% lower than the content of PI in WKY platelets; there is no difference in phosphatidylcholine (PC) and phosphatidylethanolamine (PE) contents. However, incorporation of ³H-arachidonic acid (AA) into PC was significantly higher in SHRSP platelets while those into PI and PE were lower in comparison with WKY platelets.
Aggregation responses of SHRSP platelets to lower doses of thrombin were much smaller than those in WKY platelets. With these concentrations of thrombin no significant formation of DG was observed in both platelets. In supramaximal doses of thrombin there was no difference in aggregation of SHRSP and WKY platelets; DG formation was apparently observed and it was lower in SHRSP platelets than in WKY platelets. The maximal formation of DG occurred 15sec after a thrombin stimulation.
It is concluded that reduced DG formation from PI is not responsible for attenuated responses of aggregation, secretion, and protein phosphorylation to thrombin in SHRSP platelets. With other evidence, defective Ca²⁺ functions in stimulus-response coupling appear to be an underlying mechanism for the hypofunctions in SHRSP platelets.

View full abstract

Activity of platelet-activating factor (PAF) acetylhydrolase in plasma was estimated in 35 patients with cerebral thrombosis, 18 with essential hypertension, and 34 healthy adults age-matched with two groups of patients. In all cerebrovascular patients more than 3 months had elapsed since their stroke. The assay measured the inhibition of PAF-induced platelet aggregation by the preincubation of a standard PAF solution with sample plasma. For this purpose, platelet aggregation induced by a PAF solution which had been preincubated with an equal amount of citrated plasma at 37°C for 15min was compared with that induced by a control PAF solution which had been preincubated with phosphate-buffered saline.
The average values of plasma PAF acetylhy-drolase activity in the cerebrovascular patients and the hypertensives were 4.18±3.08 and 1.71±0.27μg/ml, respectively. These values were significantly higher than the average value of plasma PAF acetylhydrolase activity in the control group: 1.51±0.51μg/ml. In each of three groups, plasma PAF acetylhydrolase activity correlated positively with the level of serum LDL-cholesterol, reflecting the complex formation of this enzyme with plasma lipoproteins, mainly with LDL. Serum LDL-cholesterol level in the cerebrovascular patients was higher than that in the control, which may account, in part, for the higher-than-normal plasma PAF acetylhydrolase activity in the patients. However, relative activity of PAF acetylhydrolase to LDL-cholesterol level was found to be higher in both patient groups as compared to the control. This result may suggest that patients' LDL contains higher activity of the enzyme than that of healthy subjects, and such a fact could be considered as one of the qualitative alterations of lipoproteins in these patients.

View full abstract

To study the pathophysiological significance of platelets in arteriosclerosis, serum lipoperoxide (s-LPO) and released platelet LPO aggregation by thrombin (p-LPO production) were measured in 20 normal subjects and in the following with arteriosclerotic diseases; 32 of ischemic heart disease (IHD), 7 of hyperlipemia (HL), 13 of diabetes mellitus (DM), 34 of hypertension (HT) and 30 of cerebral vessel disease (CVD).
Serum LPO levels were significantly higher in following groups of patients, 3.17±1.77nmol/ml in IHD, 3.63±0.62nmol/ml in HL, 4.00±2.39nmol/ml in DM, 2.93±1.19nmol/m/ in HT and 3.16±1.23nmol/ml in CVD, than in normal subjects of 1.75±0.56nmol/ml.
Levels of p-LPO production were 8.75±3.18nmol/10⁹ platelets in normal subjects, 13.15±8.71nmol/10⁹ platelets in IHD, 14.23±6.13nmol/10⁹ platelets in HL, 12.49±9.18nmol/10⁹ platelets in DM, 11.26±8.08nmol/10⁹ platelets in HT and 12.31±12.11nmol/10⁹ platelets in CVD.
Levels of p-LPO in HL were significantly higher than those in normal subjects. Positive correlation-ship between p-LPO production and s-LPO levels were observed in patients with IHD, HL, DM, HT and CVD.
In treadmill stress test, patients were divided to three groups according to % change of p-LPO production, ; i. e., Group I with increased +10% upper of p-LPO production, Group II within equivocal (±10%) of p-LPO production, and Group III with decreased -10% lower after treadmill test.
There was a reverse correlation (p<0.02) between after-before (A-B) difference of p-LPO production and those of s-LPO levels measured before (B) and after (A) treadmill stress test.
Platelet adhesiveness was significantly increased in after treadmill stress test. Maximum platelet aggregation rates to ADP, adrenaline and collagen were increased in group I, but those in group III were decreased.
In group III, there were higher p-LPO production levels and higher platelet aggregation rates before treadmill stress test than other two groups. ST depression was significant in all cases of group III after treadmill stress test.

View full abstract

Platelet function and serum lipoproteins were studied in ten patients (two males and eight females, mean age 51±12 y. o.) with hypothyroidism.
Platelet aggregation and ATP release were determined by Lumi-aggregometer using ADP, collagen and epinephrine as stimulants.
Platelet factor 4 (PF4) and thromboxane B₂ (TXB2) were determined by radioimmunoassay. HDL-cholesterol (HDL-C) was determined by heparin-manganese method. HDL subfractions were separated by gradient gel electrophoresis (PAA 4/30). Apolipoproteins were measured by single radial immunodiffusion.
Platelet aggregation increased in those patients at stimulating by epinephrine. ATP release also increased at stimulating by epinephrine. PF4 increased at stimulating by epinephrine and TXB2 increased at stimulating by ADP or epinephrine significantly (p<0.05), respectively.
Platelet aggregation was not correlated with thyroid hormones or total cholesterol. But it had a positive correlation tendency with HDL-C or HDL₂-C and a negative one with HDL₃-C.
These results suggested some relationships between platelet function and HDL metabolism in patients with hypothyroidism.

View full abstract

Hematocrit (Ht), platelet aggregability, plasma 6-keto PG F_1α, and TXB₂ of 9 Japanese climbers were investigated at 4, 700m high B. C. before and after peak (6, 794m)-attack in the area of western Tibet compared with at sea level control. Ht was increased up to 76.4% (mean) at 4, 700m, and showed 80.8% (mean) after peak-attack. Platelet aggregability was transiently increased when reaching at high altitude. Plasma 6-keto PG F_1α and TXB₂ was also increased at high altitude.
Although it is well known that man showed hemoconcentration and hypercoagulation tendency staying at high altitude due to hypoxia, there has never been the report of human platelet aggregability. Hyperaggregability of platelet at high altitude is worthy of note with special reference to coagulopathic condition of the brain and other organ during the high altitude mountaineering.

View full abstract

To clarify the mechanism of increasing platelet aggregation in ischemic diseases, the following experiments were carried out.
1) Maximum platelet aggregability (MPA) before and after O₂ inhalation were estimated in 6 patients (2 a victim of strokes, 2 a victim of old myocardial infarctions, and 1 a victim of cor pulmonale, and 1 a victim of hypertensive) who were given O₂ of 2 liter/min via nasal canal for dyspnea. After the O₂ inhalation of 60 minutes, the ADP and epinephrine induced MPAs were suppressed compared to the MPAs before the inhalation. In the collagen induced MPAs of the same above condition, a decreasing trend was recognized.
2) The ADP induced and the epinephrine induced MPAs in the venous blood showed higher trends compared to the same two kinds of MPAs in the arterial blood, but in the collagen induced MPA, there were no differences found (between the venous and the arterial blood). MPAs were measured in 6 patients; 3 of whom were victims of cerebral thrombosis, 2 of whom were victims of ischemic heart diseases, and 1 who suffered from hypertensive.
3) The MPAs in the ischemic blood (by arm ligation) were defined in 10 healthy persons. After the 5 minute legations, the MPAs were suppressed.
4) After the O₂ bubblings, the MPAs in 8 healthy persons increased.
After the N₂ bubblings the MPAs did not change significantly, but after the CO bubblings, the MPAs decreased markedly.

View full abstract

The platelet aggregation and serum lipids were evaluated in three groups, that is normal control, diabetes mellitus and liver cirrhosis. The platelet aggregation was made a comparison between one and another group using the plasma exchange method. Briefly, after centrifugation of platelet-rich-plasma, the supernatant was replaced with the platelet-poor-plasma (PPP) of another group. Platelet aggregation was performed by method of Born. In conventional method, platelet aggregation of diabetic patients was slightly increased but that of cirrhotic patients was decreased. Whereas, after plasma exchange, the aggregation of normal controls was slightly increased in diabetic PPP. Hyper LDL and hypo HDL-cholesterolemia of diabetic patients may be plasma factors on platelet aggregation.

View full abstract

The effects of native LDL and UWS-LDL on the platelet aggregation induced by ADP, collagen, and epinephrine were investigated.
1) Native LDL inhibited slightly the platelet aggregation induced by ADP or collagen, but slightly enhanced it induced by epinephrine.
2) UWS-LDL enhanced markedly the platelet aggregation in these three aggregants.
3) UWS-LDL dialyzed against flowing water for 120 hours enhanced the platelet aggregation more than that for 48 hours.
It was speculated that the interaction between platelet and UWS-LDL plays a very important role in formation and progression of arteriosclerotic lesion.

View full abstract

We evaluated activities of 5'-nucleotidase (5'-N), 3'-5'-phosphodiesterase (3'-5'-PDE), AchE, and ChAT on intraparenchymal blood vessels of a human brain. Brain vessels were isolated using the method which we developed. Fragments of human brain weighed 2 or 3g were minced and passed through 250μm nylon mesh. The material on the mesh was resuspended in buffer, after mild homogenization, passed through 73μm mesh. The mesh was washed, then the fluid was passed through 150μm mesh. Two vessel fractions were separated on the mesh and in the filtrate. The fraction on the mesh consisted primarily of larger vessels greater than arterioles, and that in the filtrate consisted predominantly of microvessels, which were purified by passing through a column of glass beads and centrifuged on sucrose density gradient. We evaluated the degree of contamination of isolated vessels using cerebroside as an indicator. The cerebroside level in these fractions was less than 5 percent of that in the brain homogenate.
The activity of γGTP was significantly higher than that in the brain homogenate. These results indicate that enzyme activities are preserved well during the isolation procedure. 5'-N level was significantly lower in these fractions. 3'-5'-PDE level was significantly higher in the large vessel than in the small vessel fraction. Changes of these enzyme activities in the vessels may affect micro-circulation and blood brain barrier function via change in the concentration of adenosine and cyclic AMP. ChAT activity was very low in vessel fractions. AchE activity was significantly higher in both vessel fractions than in the brain homogenate, and in small vessel fraction than in the large vessel fraction. The discrepancy of these two enzyme activities in isolated vessels will provide a new tool and scope in studies on brain microvessels.

View full abstract

The activity of the angiotensin-converting enzyme (ACE) was measured in serum and brain microvessels of adult stroke-prone spontaneously hypertensive rats (SHR-SP), stroke-resistant spontaneously hypertensive rats (SHR-SR) and Wistar Kyoto Rats (WKY). In brain microvessels, SHR (SHR-SR+SHR-SP) were found to have reduced ACE activity as compared to WKY. Furthermore the activity of this enzyme was significantly lower in SHR-SP than that in SHR-SR. ACE activity was inversely related to the systolic blood pressure. γ-GTP activity and prostaglandin I₂ release, either basal or stimulated with arachidonic acid, from isolated brain microvessels were similar in the three groups. Serum ACE activity was greatly decreased in SHR. In contrast to brain microvessels, SHR-SP showed higher activity than SHR-SR and the difference was significant. There was no correlation in ACE activity between serum and brain microvessels. The marked reduction of ACE activity in brain microvessels of SHR-SP may be relevant to the endothelial damage or the pathogenesis of vascular lesions in that animal model.

View full abstract

The purpose of this study was to examine the progressive and regressive changes in peripheral arterial elasticity in experimental hypercholesterolemic rabbits and the effects of anti-atherosclerotic drugs, such as pantethine and elastase, on these changes.
Rabbits were divided into 4 groups and given the following diets: Group 1, high cholesterol diet (HCD) for 12 weeks; Group 2, HCD and pantethine or elastase for 12 weeks; Group 3, HCD for 12 weeks and then normal diet (ND) for 12 weeks; Group 4, HCD for 12 weeks and then ND and pantethine or elastase. The arterial elasticity in the rabbit forearm was measured photoplethysmographically every two weeks.
The arterial elasticity in group 1 began to change after 4 weeks of HCD and decreased gradually. After 12 weeks of feeding HCD, average arterial elasticity was about 30% lower than the base-line value. The arterial elasticity in group 2, however, showed little changes during the course of HCD (p<0.01). These findings indicated that the progression of experimental atherosclerosis was suppressed by administration of pantethine or elastase.
The decreased arterial elasticity in rabbits fed on HCD recovered gradually after return to the normal diet in group 3 and 4. The degree of recovery in group 4 given pantethine or elastase was similar to that in group 3.
These data suggest that the noninvasive measurement of the elastic property used in this study can provide useful informations about the progressive and regressive changes of peripheral atherosclerosis in experimental hypercholesterolemic rabbits and that pantethine and elastase may have preventive effects on these atherosclerotic changes.

View full abstract

In atherosclerotic lesions the lipid (mainly cholesterol ester) and Ca content of elastin fr, increased progressively with increasing severity of atherosclerosis. Autoclave purified elastin fr. derived from areas of plaque in human arch to thoracic aorta was more polar in amino acid residues than similarly prepared elastin fr. from adjacent or non-plaque areas of same aorta. The polarity of the elastin fr. after purification with EDTA, BrCN and Urea was lower than those before the treatment. Those change in amino acid composition reflected some contamination of the elastin fr. The treatment due to decalcify and not to change lipid deposition in plaque areas, and the presence of the acidic component in tropoelastin preparations can explain the variation of amino acid of the elastin fr.
It may be suggested that heterogenicity of elastin fr. and tropoelastin preparation in plaque could be one of the factors of Ca and lipid deposition in atherosclerosis.

View full abstract

The role of collagens on human umbilical vein endothelial cell (HUV-EC) growth was investigated. Any type of collagens (type I, II, III, IV, V), coated on culture dishes, facilitated to proliferate HUV-EC without any growth factor. HUV-EC proliferated more efficiently on the type I or IV collagen coated dishes with endothelial cell growth supplement (ECGS). The optimum dose of collagens for EC growth was seen (4-40μg/well) and EC growth was inhibited with high dose of collagens (400μg/well) even in the presence of growth factors.

View full abstract

As there may be some differences in the mechanism of the initiation and progression of the atherosclerosis between each organ artery, we studied effects of various vasoactive drugs on the cultured smooth muscle cells (c-SMC) obtained from the aorta, coronary and renal arteries of swine. Contractive effects by methacholine, noradrenaline and serotonin were examined on ultrastructural basis. The obtained results were as follows.
1) Each three kind of drugs made all c-SMC obtained from each artery contracted.
2) After contraction, there were a reduction in cell volume, and globular cytoplasmic projections, which could be divided into three categories by size.
3) Contraction activity of c-SMC was different in its intensity between each organ artery. By methacholine, the renal arteries were the most and followed by the coronary arteries in contraction intensity, and the aorta was weakest. By noradrenaline, the coronary arteries was most intensive and followed by the renal arteries and the aorta was weakest. By serotonin, the coronary arteries were similar to the renal arteries and the aorta was weaker than other two.
4) It was suggested that large-sized globular projections were correlated with perinuclear vacuoles occurred during vascular spasm in the renal arteries, reported previously by Takeuchi.

View full abstract

We observed the pathological findings induced by coronary angioplasty in human postmortem hearts.
The consequence followed as;
1) Intimal splitting was most frequent of all findings (26%).
2) The media and the intima of non atheromatous lesions were well stretched and atheromatous lesions with a hyalinized fibrous cap projected to the outside, but was not compressed. The mechanical destruction was found in lesions with severe stenosis by angiogram.
3) The mechanical destruction of intima began from 2 atm of balloon pressure and increased gradually at higher pressure.

View full abstract