Promotion of vascular smooth muscle cell growth by homocysteine: a link to atherosclerosis
Jer-Chia Tsai,Mark A. Perrella,Masao Yoshizumi,Chung-Ming Hsieh,Edgar Haber,Robert Schlegel,Mu-En Lee +6 more
TLDR
The growth-promoting effect of homocysteine on vascular smooth muscle cells, together with its inhibitory effect on endothelial cell growth, represents an important mechanism to explain homocy steine-induced atherosclerosis.Abstract:
Plasma homocysteine levels are elevated in 20-30% of all patients with premature atherosclerosis. Although elevated homocysteine levels have been recognized as an independent risk factor for myocardial infarction and stroke, the mechanism by which these elevated levels cause atherosclerosis is unknown. To understand the role of homocysteine in the pathogenesis of atherosclerosis, we examined the effect of homocysteine on the growth of both vascular smooth muscle cells and endothelial cells at concentrations similar to those observed in clinical studies. As little as 0.1 mM homocysteine caused a 25% increase in DNA synthesis, and homocysteine at 1 mM increased DNA synthesis by 4.5-fold in rat aortic smooth muscle cells (RASMC). In contrast, homocysteine caused a dose-dependent decrease in DNA synthesis in human umbilical vein endothelial cells. Homocysteine increased mRNA levels of cyclin D1 and cyclin A in RASMC by 3- and 15-fold, respectively, indicating that homocysteine induced the mRNA of cyclins important for the reentry of quiescent RASMC into the cell cycle. Furthermore, homocysteine promoted proliferation of quiescent RASMC, an effect markedly amplified by 2% serum. The growth-promoting effect of homocysteine on vascular smooth muscle cells, together with its inhibitory effect on endothelial cell growth, represents an important mechanism to explain homocysteine-induced atherosclerosis.read more
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A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes
TL;DR: Higher folic acid intake by reducing tHcy levels promises to prevent arteriosclerotic vascular disease and under different assumptions, 13,500 to 50,000 CAD deaths annually could be avoided.
Journal ArticleDOI
Endothelial Cells in Physiology and in the Pathophysiology of Vascular Disorders
Douglas B. Cines,Eleanor S. Pollak,Clayton A. Buck,Joseph Loscalzo,Guy A. Zimmerman,Rodger P. McEver,Jordan S. Pober,Timothy M. Wick,Barbara A. Konkle,Bradford S. Schwartz,Elliot S. Barnathan,Keith R. McCrae,Bruce A. Hug,Ann Marie Schmidt,David M. Stern +14 more
TL;DR: The membrane has long been viewed as an inert cellophane-like membrane that lines the circulatory system with its primary essential function being the maintenance of vessel wall permeability.
Journal ArticleDOI
Homocysteine and atherothrombosis
George N. Welch,Joseph Loscalzo +1 more
TL;DR: In 1969, McCully reported autopsy evidence of extensive arterial thrombosis and atherosclerosis in two children with elevated plasma homocyst(e)ine concentrations and homocysteine thiolactone, and it has recently become clear that hyperhomocyst (e)inemia is an independent risk factor.
Journal ArticleDOI
Plasma homocysteine as a risk factor for vascular disease: The European Concerted Action Project.
Graham Im,Leslie Daly,Helga Refsum,Killian Robinson,Lars Brattström,Per Magne Ueland,Roberto Palma-Reis,Godfried H.J. Boers,Richard G. Sheahan,Israelsson B,Cuno S.P.M. Uiterwaal,Raymond Meleady,Dorothy McMaster,Petra Verhoef,Jacqueline C.M. Witteman,Paolo Rubba,Bellet H,Jan C. Wautrecht,de Valk Hw,Sales Lúis Ac,Parrot-Rouland Fm,K.S. Tan,I.M. Higgins,Danielle Garcon,Generoso Andria +24 more
TL;DR: An increased plasma total homocysteine level confers an independent risk of vascular disease similar to that of smoking or hyperlipidemia, and compared with nonusers of vitamin supplements, the small number of subjects taking such vitamins appeared to have a substantially lower risk ofascular disease, a proportion of which was attributable to lower plasma homocy steine levels.
Journal ArticleDOI
The Response-to-Retention Hypothesis of Early Atherogenesis
Kevin Jon Williams,Ira Tabas +1 more
TL;DR: Subendothelial retention of atherogenic lipoproteins as the central pathogenic process in atherogenesis is strongly supported, and other contributory processes are either not individually necessary or are not sufficient.
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