Pathophysiological Role of Angiopoietin-2 in Human Coronary Atherosclerosis / 대한해부학회지

ABSTRACT

Neovascularization is well known to occur in human atherosclerotic plaques; however, its pathophysiological roles, mechanism, and stimuli still remain unclear. Angiopoietin-1 and -2 belong to another vascular-specific growth factor family and regulate angiogenesis. Angiopoietin-2 (Ang-2) provides a destabilizing signal for endothelial cells, leading to vessel regression or sprouting depending on the presence of other angiogenic factor. But role and distribution of Ang-2 in atherosclerosis are not well known. Thus, we studied 1) the distribution and amount of Ang-2 2) the relationship between Ang-2 expression and vascular morphometrical change 3) the relationship between Ang-2 expression and neovascularization in atherosclerotic lesions. Paraffin sections from 36 human coronary arterial segments were characterized as normal, preatheroma, atheroma, fibroatheroma and complicated lesion according to American heart association classification. Expression of Ang-2 and related factors were examined using immunohistochemistry and western blotting with antibodies against Ang-2, CD31 (endothelial cells), alpha-actin (vascular smooth muscle cells), CD36 (monocyte & macrophage), Tie-2 and VEGF. Expression of Ang-2 was not shown in normal arterial segment. Ang-2 were localized in lumen-lining endothelium, macrophage, some SMCs of atheromatous plaque in advanced lesion. Amount of Ang-2 was increased according to progression of atherosclerosis. Intraplaque microvessels had Ang-2 and VEGF positive endothelial cells and number of those in plaque increased according to progression of disease. Intimal neovascularization is correlated with intimal thickening in atherosclerotic lesion (R2 = 0.7424). Therefore, they suggest that Ang-2 has an important role in the progression of human coronary atherosclerosis, as well as in neovascularization. This study implicates Ang-2 as an important potential therapeutic target in vascular disease