Hypertension and cerebral artery: Hypertensive damage of cerebral artery occurs in the densely innervated artery; brain base vascular nets and perforating arteries, and is characterized by medial cell necrosis (moth-eaten cell atrophy and necrosis). The pilar circumflex artery, which has less frequent innervation than the perforating artery, is not involved with hypertension. A hypertensive cerebral hemorrhage is not induced by the rupture of a microaneurysm (angionecrosis), but is due to a direct rupture at the bifurcation of a hypertensively involved perforating artery. The microaneurysm indicates a recanalisation state after a subclinical rupture of a small artery less than 200μ in diameter. Hypertension may also accelerate a lipid accumulation in the intima even in the arterioles of the perforating branches demonstrating both a luminal narrowing by intimal thickening and/or dilation due to medial cell necrosis. The former causes cerebral thrombosis in the basal ganglia, while the latter loses a vascular function by earthen pipe phenomenon in the artery. They can, thus induce a disturbance of the autoregulation system regarding intracerebral circulation. As a result, leukoaraiosis occurs and extends to the white matter of the cerebrum (Bin-swanger type dementia).
Hypertension and the coronary artery: As for atherogenesis, hypertension is suppressed in the coronary artery, but coronary spasms frequently occur in variant angina which histologically reflects the adventitial inflammation of coronary artery located in the subepicardium. Accumulated inflammatory cells (lymphocytes and monocyte/macrophages) may also directly stimulate medial smooth muscle cells, and/or do so through the vascular nerve fibers in adventitia where they are densely distributed. Repeated coronary spasms may also accelerate atherosclerosis in the intima by an increased insudation of the same artery.
Hypertension and renal artery: Hypertensive vascular damage occurs in the interlobular and afferent arteries measuring 50-100μ in diameter, which are densely innervated by adrenergic & cholinergic fibers, demonstrating with either medial cell necrosis or moth-eaten atrophy. Those changes thus result in a reduced autoregulation system for glomerular circulation, and may also induce glomerulosclerosis by both ischemic and glomerular hypertension (hyperfiltration) mechanisms.

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A characteristic of atherosclerosis is the accumulation of large amount of lipids, mainly cholesteryl ester, in arterial walls. These lipids accumulate in the extracellular space or in the cytoplasm of lipidladen cells. To understand mechanisms by which these lipids accumulate in arterial walls, we prepared a novel monoclonal antibody (ASH1a/256C) which recognized the region of fatty streaks in atherosclerotic aortae both in human and WHHL rabbits. The antibody recognized especially the surface area of fatty streaks, suggesting that the antigenic material was associated with the endotherial cells located on the fatty streaks. The amount of antigenic material detected by ELISA was almost 8 times higher in atherosclerotic aorta than in normal aorta. Since the antigenic material was extracted by acetone and was presumed to be a glycolipid, reactivity of the antibody to various gangliosides and related compounds was examined. The antibody reacted strongly with asialo GM2 and less with asialo GM1. The reactivity to asialo GM2 was 5 times higher than to asialo GM1. The antibody, however, did not react with other gangliosides such as GMI-4, GD1a, GT1b and lactosyl ceramide. Gangliosides of globo family, mono and polysaccharides, heparan sulfate, chondroitin sulfate had no reactivity either. To examine that the antigenic material in atherosclerotic lesions was asialo GM2 itself or similar compounds, the acetone extract prepared from the lesions was applied an a slica gel TLC and immunostaining was carried out. The antibody reacted with four compounds, one of which corresponded to asialo GM2, suggesting that atherosclerotic lesions contain asialo GM2 itself and three novel compounds which possess similar epitope of asialo GM2.
We have also produced a monoclonal antibody (EMR1a/212D) which specifically recognizes the extracellular regions where lipids deposit in atherosclerotic aorta. The antigenic material of this antibody was revealed to be vitronectin, a 66kDa glycoprotein. To investigate molecular species of vitronectin in atherosclerotic lesions, a new monoclonal antibody (EMR1b/244H) which recognized peptide region of vitronectin was prepared. Using the both antibodies, 56, 50 and 47kDa vitronections were found in atherosclerotic lesions together with 66kDa vitronectin which is a major component in serum. The 56 and 50kDa vitronectin were major component in atherosclerotic lesions and increased markedly with developmant of atherosclerosis.
Based on our findings, we will discuss roles of endotherial cells and vitronectin in accumulation of lipids in arterial walls.

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Fibronectin, type I, type IV, and type V collagens were compared for their abilities to promote mouse peritoneal resident macrophage adherence, and the effect of aging on macrophage adhesion to these matrix proteins was examined. Adherence of macrophages to fibronectin was remarkable and more than 5-fold compared to type I, type IV or type V collagens. Adherence of macrophages to fibronectin and type I collagen increased during aging. However, no age-related changes were observed in macrophage adherence to type IV and type V collagens. The percent of inhibition of macrophage adherence to fibronectin by arginine-glycine-aspartic acid-serine (RGDS) peptide (58.1±2.7%) was significantly (P<0.01) higher than that in cells from young mice (23.1±5.7%). These data suggest that macrophage attach preferentially to fibronectin and that the ability of macrophage to attach to fibronectin increases during aging. The age-related increase in macrophage attachment to bibronectin is related to the concentration of cell surface receptors of macrophage which recognize RGDS sequence within fibronectin during aging. Adherence of macrophage to fibronectin implies retention of macrophages in subendothelial space. Age-related increase in macrophage ability to attach to fibronectin may be related to atherogenesis during aging.

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Ultrasound highresolution B-mode imaging was conducted on the carotid arteries of normal volunteers and dabetic patients to non-invasively determine the average thickness of the intimal and medial complex (avgIMC). In normal volunteers, avgIMC is 0.43±0.06mm (7-19 yr) and 0.87±0.09mm (50-59 yr), and does not exceed 1.1mm. The AvgIMCs of diabetics were significantly higher than those of normal volunteers over the all age groups. The avgIMC of diabetics with cerebral T₂-prolonged regions, determined by MRI, was significantly higher than that of in diabetics without regions. Multivariate regression analysis on 566 NIDDMs showed age, hiht nonHDL-cholesterol, smolking, duration of diabetes, high systolic blood pressure and low HDL-cholesterol to be related to the progress of avgIMC. Similar study on 114 IDDMs aged 7-29 show both age and duration of diabetes to be related to the progression. Diabetics with averaged HbAlc>7.5% showed negligible change in avgIMC. Diabetics with averaged HbA1c>9.5% showed significantly higher change.
It is concluded that average thickness of intimal and medial complex of the carotid artery determined by ultrasound high resolution B-mode imaging is useful as a quantitative indicator of atherosclerosis. Aging and diabetes independently progress carotid atherosclerosis of adult NIDDM adult and young IDDM. Negligible change of avgIMC in diabetics with low HbA1c levels indicates that strict glycemic control could arrest carotid atherosclerosis in diabetics.

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We examined lipoprotein polyacrylamide gel (PAG)-disc electrophoresis in 82 survivors of myocardial infarction (OMI) and in 20 controls in order to elucidate the relationship between lipoprotein disorders and the incidence of myocardial infarction. PAG-disc electrophoretic patterns were classified into one of four groups according to differences in the shape of the LDL portion: type S (symmetrical), type A (asymmetrical), type N (nodular) and type D (disrupted). The frequency of these S, A, N, D patterns in the OMI group was compared to that in the control group. We also assessed serum lipids, lipoproteins and Lp (a) levels in the OMI group and we compared them in each S, A, N, D group. Statistical analysis was performed by oneway ANOVA and X² test.
In the OMI group, type S was significantly less frequent than in the control (p<0.001), while type N was significantly more frequent than the control (p<0.001). Type D was found only in the OMI group. With respect to serum lipids, apolipoproteins and Lp (a) levels, total cholesterols were distributed almost evenly across the S, A, N, D groups. Triglyceride levels facross were significantly higher in group N than in group S (p<0.05). In group D, triglyceride levels were significantly higher than in groups S (p<0.001), A (p<0.001) and N (p<0.001), respectively. HDL-cholesterol levels were significantly lower than those of type S (p<0.01) and A (p<0.01). Serum levels of apoprotein CII, CIII, and E in groups N and D were higher than those of type S (p<0.05). In group D, serum levels of apo E were significantly higher than in groups S (p<0.001), A (p<0.001) and N (p<0.00 1), respectively. Type IIb and IV hyperlipidemias appeared with significantly higher in groups N and D than type IIa and control groups, and these tendency was more dominant in type D.
These data suggest that lipoprotein disorders clarified by PAG electrophoresis are closely related in the incidence of myocardial infarction. These disorders are accompanied by hypertriglyceridemia, low levels of HDL-cholesterol and high levels of apo CII, CIII and E. Therefore, lipoprotein disorders includeing TG-rich remnants play an important role in the incidence of myocardial infarction even in cases of normolipidemic serum.

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Seven patients with hypertriglyceridemia were studied. Those patients consisted of 2 type IIb and 5 type IV hyperlipidemia. The patients were given 600mg/day or 1200mg/day of clinofibrate every day for 4-12 weeks. The lipoproteins were fractionated by ultracentrifugation by Hatch and Lees' method before and after clinofibrate treatment.
In each lipoprotein fraction, TG, Chol and ApoB were measured. Plasma triglyceride decreased by 37.3% and VLDL-TG by 39%. Total cholesterol decreased by 12.6% and VLDL-Chol by 52%. IDL-Chol decrased by 32.5%. VLDL-Apo B decreased significantly. The results indicate that Clinofibrate treatment reduced Chol, TG and Apo B content in VLDL, and that treatment decreased the number of VLDL particles.

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