Homocysteine smooth muscle proliferation

Carmody et al. found that the addition of homocysteine to a culture of vascular smooth muscle cells resulted in a dose-dependent increase in DNA synthesis and cell proliferation, but vitamins B6 and B 2 alone did not substantially inhibit the effect of homocysteine. However, the addition of folic acid resulted in significant inhibition of DNA synthesis (64). Rosiglitazone has been shown to reduce serum tHcy levels, smooth muscle proliferation, and intimal hyperplasia in Sprague-Dawley rats fed a diet high in methionine (65). 

Is homocysteine involved in the pathogenesis of restenosis An association between homocysteine and restenosis is not unlikely, given the fact that homocysteine appears to induce inflammation, impair endothelial function, and stimulate smooth muscle proliferation all these mechanisms are potentially implicated in the development of restenosis. However, the data regarding tHcy levels and the risk of restenosis after coronary angioplasty are conflicting. Some investigators found an increased risk of restenosis after PCI in patients with high plasma levels of homocysteine, especially in patients not treated with stents (70-72), whereas others did not find any increased risk either in patients with (73-75) or without stents (76). 

Murthy SN, et al. Rosiglitazone reduces serum homocysteine levels, smooth muscle proliferation, and intimal hyperplasia in Sprague-Dawley rats fed a high methionine diet. Metabolism 2005 54 5) 645-652. 

Homocysteine blood levels (>15 jtmol/L) promote atherosclerosis, perhaps by stimulating proliferation of arterial wall smooth muscle cells. Supplementing the diet with folic acid can reduce high levels. Lpa is a mod-ihed LDL particle that is both atherogenic and pro-thrombic. 

Buemi et al. reported that the addition of Hey to the medium of smooth muscle cells in tissue culture caused a significant increase in cell proliferation and death through apoptosis and necrosis. When folic acid was added to the culture medium, homocysteine concentrations in media were reduced and the effects of Hey on the proliferation/apopto-sis/necrosis balance of cells in culture were inhibited (62). Ozer et al. (63) showed that the MAPK kinase pathway is involved in DNA synthesis and proliferation of vascular smooth muscle induced by homocysteine. 

Buemi M, etal. Effects of homocysteine on proliferation, necrosis, and apoptosis of vascular smooth muscle cells in culture and influence of folic acid. Thromb Res 2001 104(3) 207-213. 

Kartal Ozer N, Taha S, Azzi A. Homocysteine induces DNA synthesis and proliferation of vascular smooth muscle cells by interfering with MAPK kinase pathway. Biofactors 2005 24(1-4) 193-199. 

Carmody BJ, et al. Folic acid inhibits homocysteine-induced proliferation of human arterial smooth muscle cells. J Vase Surg 1999 30(6) I 121-1 128. 

Homocysteine Increase of vascular fragility, loss of endothelium, proliferation of smooth muscle cells promotion of atheroma formation Atherosclerosis synthesis... 

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