Sterodid hormones raise the serum cholesterol level and promote the process of atherosclerosis. The progression of atherosclerosis was suppressed when steroid hormones were administrated to cholesterol-fed rabbits.
Platelet-derived growth factor (PDGF) is a smooth muscle cell proliferating factor and it also participates in wound healing due to the proliferation of fibroblasts. It is also known that in patients treated with steroid hormones, the wound healing is delayed and the number of macrophages in wounds is reduced.
From these findings, the following hypotheses are proposed:
(1) Sterod hormones suppress the differentiation of macrophages.
(2) Steroid hormones inhibit the expression of PDGF in macrophages.
To confirm these hypotheses, we examined the effect of dexamethasone (DEX) on the differentiation and the PDGF expression in a monocytic leukemia cell line, THP-1. DEX inhibited the cell adhesion and NBT reducing activity of THP-1 cells treated with phorbol myristate acetate (PMA). EDX exerted a morphological effect on PMA-stimulated THP-1 cells by suppresing the development of the characteristic spreading shapes in differentiated macrophages. The levels of the PDGF-A and -B mRNA were determined by reverse transcription (RT)-PCR methods. DEX inhibited the expression of PDGF-A during PMA stimulation in a dose dependent manner. PDGF-A expressions were suppressed within 6 hrs to 24 hrs following administration of DEX. Little PDGF-B mRNA was detected in PMA treated THP-1 cells and the effect of DEX could not be detected, suggested that DEX may partially inhibit the differentiation and the PDGF-A expression in monocytes and prevent the progression of atherosclerosis.

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Serum fatty acids analyses were performed on subjects in their thirties and fifties living in urban Japan. It is known that the Japanese traditionally consume relatively large amounts of omega-3 polyunsaturated fatty acids from fresh fish, and this may, in part, contribute to their low incidence of coronary heart disease (CHD).
This study was performed to examine the differences of the composition of serum fatty acids (omega-3 and omega-6 ratio) between young and senior people. We surveyed plasma fatty acids in 176 people in their thirties and fifties living in Tokyo. The level of serum cholesterol was 198mg/dl in the first group and 222mg/dl in the second group. The percentage of omega-3 polyunsaturated fatty acids in the total serum fatty acids was 7.01±1.6% in the younger group and 9.67±1.8% in the elder group (p<0.01). The omega-3/omega-6 ratio was 0.19±0.05 and 0.29±0.09 (p<0.01), respectively.
These findings suggest a significant difference in eating habits between young and elderly generations in Japan. A trend in the lower of omega-3 fatty acids from fish meat in the younger generation could be an important factor in the possible increase in occurrence of coronary heart disease in Japan's future.

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The development of the atherosclerotic lesion is associated with neovascularization in the thickened intima and media of vascular walls. Neovascularization may have a role in the progression of atherosclerotic plaque as well as in the development of the plaque instability and the intraplaque hemorrhage. Further vasa vasorum could be potentially involved in vasospasm at the plaque site. However, the mechanism and stimulus for neovascularization in the atherosclerotic plaque are unknown. We postulated that smooth muscle cells (SMCs) and macrophages, major cellular components in the atherosclerotic lesion, might contribute to the induction of neovascularization through the secretion of an angiogenic factor.
Vascular endothelial growth factor (VEGF) is an endothelial cell-specific and an angiogenic factor in vivo. VEGF expression was enhanced by hypoxia in human smooth muscle cells and peripheral mononuclear cells. Free radical, which may be generated in the ischemic tissues by activated granulocytes and macrophages, and ischemia/reperfusion, also increased VEGF mRNA levels. Furethermore, lysophosphatidylcholine stimulated VEGF expression on the human SMCs via intracellular oxidative stress. These data suggest that VEGF may be a potent inducer of angiogenesis in the atherosclerotic lesion.

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Transforming growth factor-β (TGF-β) is synthesized and secreted as inactive high molecular weight complex (large latent complex). In this complex, TGF-β molecule is non-covalently associated with a latency associated peptide (LAP) and a third component denoted the latent TGF-β binding protein (LTBP) containing 17 EGF-like repeats and 4 LTBP specific eight cysteine repeats. It is reported that TGF-β is a bifunctional regulator of the migration and proliferation of arterial smooth muscle cells (SMC) in vitro, and enhances intimal thickening of a balloon catheter (BCI) injured artery by the increase of extracellular matrix in vivo. LAP has an essential role in latency of TGF-β, but the function of LTBP is not known in an artery. In this study, we report on the role of LTBP in the formation of atheromatous lesions in an artery. 100pg/ml-2ng/ml of LTBP stimulated the migration activities of cultured rat SMC about 5-7 times compared with control. The maximal activity of SMC migration by LTBP was 75% of that by 10ng/ml of PDGF-BB, and the migration by LTBP was chemotaxis with unidirection by a checker board analysis. By cross-linking and immunoprecipitation experiments, ¹²⁵1-LTBP was bound to the surface of SMC, suggesting that at least part of LTBP directly binds to SMC and expresses the migration activity. Furthermore, LTBP was expressed in the intimal layer of BCI injured artery stronger than in the medial layer. These results suggest that LTBP has an important role in the initial stage of arterial intimal thickening through the acceleration of SMC migration from the medial to the intimal layer of an artery.

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To clarify the clinical significance of lipoprotein lipase mass in preheparin serum (preheparin LPL mass), its relationships with serum lipoproteins in 305 persons taking healthy check, the values in diabetic patients (n=36) as insulin deficient state and the value changes during bezafibrate administration in hypertriglyceridemic patients (n=40).
Preheparin LPL mass was not necessarily correlated well with postheparin plasma LPL mass. Preheparin LPL mass was negatively correlated with serum triglyceride levels, and positively with HDL cholesterol levels, but, not with total cholesterol levels in persons taking health check.
Preheparin LPL mass was negatively correlated with HbAlc in diabetic mellitus patients.
Preheparin LPL mass increased by administration of bezafibrate in hypertriglyceridemic patients.
From these results, it is suggested that preheparin LPL mass might be reflecting the amount of functioning LPL in the body. Namely, preheparin LPL mass might be one of the indicator of the LPL production rate in the individuals.

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