Abstract
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.
