Atherosclerosis, growth factor study

Stephanidis C, Toutouzas K, Stefanadi E, et al. Inhibition of plague neovascularization and intimal hyperplasia by specific targeting vascular endothelial growth factor with beva-cizumab-eluting stent an experimental study. Atherosclerosis 2007 in press. 

Proliferation and migration of vascular smooth muscle cells (VSMC) is one of the hallmarks of atherosclerosis. Red wine polyphenols hinder the proliferation and migration of cultured SMCs stimulated by growth factors through inhibition of PI3K activity and p38 (MAPK) phosphorylation.In support, resveratrol reversibly arrests VSMC proliferation in early S phase of the cycle. Recent studies on SMCs demonstrate the anti-atherogenic actions of resveratrol via its ability to inhibit the autocrine secretion and the mitogenic effects of endothelin-... 

A more frequent complication is restenosis of the angioplasty site which occurs in 25-30% of patients over 6-9 months " . Pathological studies in patients with recurrence of symptoms are infrequent but demonstrate proliferation of fibroblasts and vascular smooth muscle cells overlying and distinct from the traumatized atherosclerotic plaque . Similar lesions have been described in early atherosclerosis and there is evidence to suggest a role for platelets in the development of such lesions , possibly through release of platelet-derived growth factors which stimulate fibroblast and vascular smooth muscle proliferation . Thus, depletion or inhibition of platelets prevents the development of atherosclerosis in animal models and aspirin inhibits the accelerated coronary atherosclerosis which occurs in cardiac transplant recipients. Furthermore, restenosis is more frequent when there is evidence of a thrombus at the angioplasty site consistent with previous... 

Previously, it has been suggested that protein kinase C isoform zeta (PKCQ is directly activated by ceramide and that this interaction mediates the activation of nuclear factor-KB and stress-activated protein kinases (Bourbon et al, 2002). Subsequent studies have implicated the activation of PKC in ceramide-mediated inhibition of the serine/threonine kinase Akt (also known as protein kinase B) and growth arrest in vascular smooth muscle cells (Bourbon et al, 2002). It was thus put forth that ceramide-mediated growth suppression may play a critical role in the prevention of atherosclerosis or restenosis as a result of vascular wall stress. 

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