Immunohistochemical expression of vascular endothelial growth factor vascular permeability factor in atherosclerotic intimas of human coronary arteries

Neovascularization is well known to occur in human atherosclerotic plaques; however, its pathophysiological roles, mechanisms, and stimuli in atheroge nesis still remain unclear. In this study, 525 tissue blocks of coronary ar tery tissue obtained at autopsy from 48 patients ranging in age from 20 to 93 years old (mean+/-SD, 71+/-15 years) were immunohistochemically examined for vascular endothelial growth factor (VEGF) expression in the atheroscle rotic intimas. The atherosclerotic lesions were histopathologically classif ied into types I through VI, as proposed by the American Heart Association Committee, and the numbers of intimal blood vessels and VEGF-positive cells were then morphometrically counted in sections that were immunohistochemic ally examined with anti-CD34 and human VEGF antibodies, respectively. The m ore the atherosclerotic lesion type advanced, the more often the lesion con tained intimal blood vessels, which were expressed as percentages of the in timal section with intimal microvessels, viz, diffuse intimal thickening (D IT): 0% (0/111); type I, 31% (32/104); II, 42% (10/24); III, 66% (77/117); IV, 72% (48/67); V, 79% (70/89); and VI, 100% (13/13), P<0.0001. The number of VEGF-positive cells per intimal section was also positively correlated with the number of intimal blood vessels (P<0.0001). The VEGF-positive cell s were scattered in the fibrous caps as well as the shoulders and deeper ar eas of the plaques, and the double-immunostaining method revealed that the VEGF-positive cells were largely spindle-shaped, smooth muscle cells with s ome macrophage-derived foam cells. These findings thus suggest the possibil ity that the VEGF expressed by the smooth muscle cells and foamy macrophage s in the atherosclerotic intimas can act as a local and endogenous regulato r of endothelial cell functions, including intimal neovascularization, in a therosclerotic lesions of human coronary arteries.