Serum HDL subfractions of moderate hypertriglyceridemic patients (triglyceride [TG]: 230-350 mg/dl) with mono- and polydisperse low density lipoprotein (LDL) were analyzed by 8.5% polyacrylamide gel disk electrophoresis (PAGE) and the differences in their levels and patterns were investigated for the purpose to clarify the relationship between the LDL polydispersion and HDL subfractions.
Patients were separated into four groups by the LDL patterns on 3% PAGE and by HDL-cholesterol levels. Monodisperse- and polydisperse LDL groups were divided into normo- and hypo-HDL cholesterolemia, respectively.
In conclusion, 1) In the group with polydisperse LDL or hypo-HDL cholesterolemia, small-size HDL subfractions were increased and large-size HDL subfractions were decreased, and on the whole, it was recognized that their HDL size was inclined to decrease compared to that in normo-HDL cholesterolemia with monodisperse LDL group.
2) In the hypertriglyceridemia groups with both of normo- and hypo-HDL choles erolemia, it was found that HDL2a in the large HDL subfractions was reduced, and HDL2b of the largest HDL subfractions and HDL3c of the smallest HDL subfractions were reversely increased beyond the levels in normo-triglyceridemia. On the whole, it was recognized that HDL subfractions were inclined to become flatter than those in normotriglyceridemia.
3) In patients whose serum TG was reduced by dietary treatment (restriction of total calories and sugar content), the ratios of small-size HDL subfractions (HDL3b, HDL3c) were decreased and those of HDL2a were increased with a change from polydisperse LDL to monodisperse LDL. However, mean HDL sizes were not significantly changed after dietary treatment.

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Migration of medial smooth muscle cells (mSMC) into the intima is one of pivotal phenomena in atherogenesis. It is crucial for the migration of mSMC to be released from the extracellular matrix surrounding them by proteases. We have identified that the migrating cells after balloon injury express elastase II mRNA by in situ hybridization.
Endothelial cells, some mSMC and adventitial fibroblasts of the carotid artery and aorta in intact rats expressed elastase II mRNA. After balloon injury, the number of mSMC expressing elastase II mRNA increased obviously, in a biphasic pattern with peaks at 12 hours and 3 days after the injury. BrdU-labeled mSMC and the migrating cells expressed strongly elastase II mRNA. Internal elastic laminae adjacent to the migrating cells which expressed elastase II mRNA were ruptured. Under a transmission electron microscope, the migrating cells were characterized by a synthetic phenotype. Elastic fibers and collagen fibers in the media were reduced resulting in decreased c ntact plaques of mSMC with elastic fibers. This study suggested that elastase synthesized by mSMCs plays an important role in neointima formation after balloon-injury.

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During a total of 518 coronary bypass surgery cases, we encountered 144 incidence (28%) of muscle briges overriding the coronary artery. Of these 144 cases, we found 111 in the left anterior descending coronary artery (77%). As opposed to the control group, the muscle bridge group was found 32% more in the female-to-male ratio, which suggests atherosclerotic progressive factors for female patients. During coronary bypass grafting, we preferred to excise muscle bridges and select this as the site of graft-to-coronary bypass anastomosis, due to the absence of atherosclerosis within this segment. By constructing a mock circuit, which contains a muscle bridge that was actuated by compressing a silastic tube periodically, we observed movement of microspheres using a microscope and a high-speed video system. We suspected, based on the movement of microspheres, the possibility of intimal cell damage. We concluded that muscle bridges are one of the contributing factors of atherosclerotic progression, particullarly in the region of the left anterior descending coronary artery.

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The relationship between apolipoprotein (Apo) E phenotypes and the levels of apolipoprotein in school children (12∼13years of age) subjects and investigated. Apo E phenotypes were detemined by isoelectric focusing and immunoblotting.
The frequencies Apo E phenotypes in the population were 69.9% for E3/3, 18.7% for E4/3, 9.0% for E3/2, 1.4% for E4/2, 0.7% for E4/4 and there was no type for E2/2. There was no difference was noted in height, weight or percentage of standard body weight due to Apo E phenotype.
The levels of apo B and apo B/AI ratio were high in the Apo E4 group, intermediate in the Apo E3 group, and low in the Apo E2 group, whereas Apo E levels were low in the apo E4 group, intermediate in the apo E3 group, and high in the apo E2 group.
These results suggest that Apo E4 contributes to a predisposition to ward atherosclerosis. Apo E4 must induce much greater alteration in therisclerosis promotion due to apolipoprotein compared with Apo E3, E2. We conclude taht the Apo E phenotype prov des important genetic information for the prevention of atherosclerosis from the infantile period.

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We investigated the effect of simvastatin (Simv) on high density lipoprotein cholesterol (HDL-C) in 23 hypercholesterolemic patients who had been pretreated with probucol (Prob). Prob significantly reduced total cholesterol (TC) and HDL-C, but did not significantly decrease low density lipoprotein cholesterol (LDL-C), but additional administration of Simv along with probucol (Prob+Simv) induced further significant decreases in TC and LDL-C as well as a significant reduction in triacylglycerol (TG). Addition of Simv increased HDL-C, but this increase was not significant and HDL-C was still significantly lower than the baseline value. As we have previously reported, Simv tends to decrease high HDL-C. Therefore, we examined its effects in 21 patients with HDL-C less than 81mg/dl; two patients whose HDL-Cs increased up to more than 90mg/dl after treatment with Prob were omitted. In these 21 patients, Simv significantly increased HDLC, though it remained significantly lower than the baseline value. In lipoprot in fractions from 23 patients, Prob significantly reduced VLDL- and HDL-C. Prob+Simv significantly reduced LDL-C and VLDL-TG compared with the baseline or Prob, and significantly reduced HDL-TG compared with the baseline. In apolipoproteins, Prob significantly reduced apoA-I and significantly increased apoE compared with the baseline. Prob+Simv significantly decreased apoB, apoC-II, and apoC-III compared with the baseline or Prob, and significantly decreased apoE which had been elevated by Prob. The addition of Simv increased apoA-I, but the increase was not significant. Prob significantly increased the ratios of (TC-HDL-C)/HDL-C and apoB/apoA-I, atherogenic indices, while the addition of Simv significantly decreased these ratios. Prob significantly decreased the ratio of HDL-C/ apoA-I, while the addition of Simv increased the ratio, abolishing the significant difference from the baseline. The change in HDL-C by addition of Simv was negatively correlated with HDL-C and apoA-I after treatment with Prob, and the changes in HDL-C and VLDL-C by Prob, and positively correlated with LDL-TG after treatment with Prob. In correlation with compositional indices of HDL, the change in HDL-C by Simv was positively correlated with the change in apoA-I, the ratio of apoA-I/apoA-II, and the ratio of HDL-C/apoA-I, and was not correlated with the change in apoA-II. These data indicate that Simv can counter the Prob-induced HDL-C decrease, appearing as if Simv restored the original HDL-C levels disturbed by Prob, if HDL-C was not extremely high. Based on the findings that this Simv-induced increase in HDL-C was associated with decreases in VLDL-lipids and VLDLapolipoproteins and that an increase in HDL₂ fraction was implied, we conclude that Simv increased HDL-C by promoting VLDL metabolism. The precise mechanism of this Simv-induced increase in HDL-C remains to be further investigated. Additional-administration of Simv to reduce high serum cholesterol (LDL-C) may be highly useful especially for patients with low HDL C levels.

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To clarify whether vascular dysfunction is present in patients with non-insulin-dependent diabetes mellitus (NIDDM) without clinical evidence of peripheral vascular disease (PVD), both pulsatility index (PI; indicating a determinant of arterial distensibility) determined by high-resolution ultrasonography and ankle pressure index (API) after leg exercise and sublingual nitroglycerin (NTG; causing endothelium-independent vasodilatation) were measured in ankle vessels of 63 patients with NIDDM and 37 age- and gender-matched healthy control subjects. The diabetic patients were subdivided into two groups according to the PI value at the baseline; Group A (PI≥6.52, n=31) and Group B (PI<6.52, n=32). There were no significant differences between Group A and B in age, gender, known duration and treatment of diabetes, and the frequency of smoking, hypertension and diabetic retinopathy. However, the frequency of albuminuria was higher in Group B. There were no differences found in the responses of PI and API to leg exercise within the groups, whereas both indices increased significantly (p<0.05) in the control group after exercise. Vascular responses to sublingual NTG load were analyzed in 22 of 63 patients (Group A: n=10, B: n=12) and 31 of 37 control subjects. No differences were noted in any other clinical characteristics among the groups, except that the mean HbA₁c and triglyceride (TG) levels were significantly (p<0.05) higher in Group B than in Group A. Both the PI and API were significantly (p<0.05-0.01) decreased in Group B after loading, whereas those in control subjects and Group A remained unchanged after loading. In addition, a direct correlation was found between changes (Δ) in PI and basal TG levels in Group B. These results suggest that in patients with NIDDM uncomplicated by overt PVD, the PI may be an indicator that enables objective assessment of vascular dysfunction at an early stage of atherosclerosis, and that vasodilation in response to sublingual NTG, a smooth muscle-dependent vasodilation, may be blunted in diabetic patients with occult PVD as evidenced by decreased PI values in our series.

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Data measured for parameters of biological functions and metabolism always present some variations, arising from physico-biochemical fluctuations within the body, technical errors in measurements, instability in instruments, and limitation of the methods employed. Statistically, these variations in data are evaluated by such indices as standard deviation (SD), standard error (SE), coefficient of variation (CV) and logarithmic (geometric) standard deviation (sigma-x). When we use sigma-x to analyze variations in data gained from populations (n<100), it shows unique characteristics ; i) it indicates the extent of variations shown by individuals in a population; ii) it is an anonymous value without dimension of measured unit; iii) it is not influenced by the value of the mean data and iv) each parameter has its own fixed sigma-x value independent of the population studied, gender concerned, and method of measurement used. Therefore, it is said to be a quasi-constant value for each parameter. To ascertain the e characteristics of sigma-x, we examined a total of 20, 200 subjects (10, 599 males and 9, 601 females) from 8 populations (Muroran-Noboribetsu 1, 787, Iwate 5, 326, Shibuya-Tokyo 1, 384, Mitaka-Tokyo 1, 998, Niigata 2, 230, Wakayama 1, 878, Anan-Tokushima 1, 887, and Miyazaki 3, 710) for the sigma-x of total cholesterol, triglycerides and HDLcholesterol. Sigma-x of total cholesterol was 0.08, triglycerides 0.22, and HDL-cholesterol 0.11. These sigma-x values were nearly constant throughout subpopulations, did not differ between males and females, and were independent of methods used for measurements. Thus, individual variabilities of the parameters of lipid metabolism demonstrated their own quasi-constant values.

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