VASCULAR ENDOTHELIAL GROWTH-FACTOR (VEGF) EXPRESSION IN HUMAN CORONARY ATHEROSCLEROTIC LESIONS - POSSIBLE PATHOPHYSIOLOGICAL SIGNIFICANCE OF VEGF IN PROGRESSION OF ATHEROSCLEROSIS

Background-Vascular endothelial growth factor (VEGF) is an important a ngiogenic factor reported to induce migration and proliferation of end othelial cells, enhance vascular permeability, and modulate thrombogen icity. VEGF expression in cultured cells (smooth muscle cells, macroph ages, endothelial cells) is controlled by growth factors and cytokines . Hence, the question arises of whether VEGF could play a role in athe rogenesis. Methods and Results-Frozen sections from 38 coronary artery segments were studied. The specimens were characterized as normal wit h diffuse intimal thickening, early atherosclerosis with hypercellular ity, and advanced atherosclerosis (atheromatous plaques, fibrous plaqu es, and totally occlusive lesions). VEGF expression as well as the exp ression of 2 VEGF receptors, flt-1 and Flk-1, were studied with immuno histochemical techniques in these samples at the different stages of h uman coronary atherosclerosis progression. The expression of VEGF mRNA was also studied with reverse transcription-polymerase chain reaction . Normal arterial segments showed no substantial VEGF expression. Hype rcellular and atheromatous lesions showed distinct VEGF positivity of activated endothelial cells, macrophages, and partially differentiated smooth muscle cells. VEGF positivity was also detected in endothelial cells of intraplaque microvessels within advanced lesions. In totally occlusive lesions with extensive neovascularization, intense immunost aining for VEGF was observed in accumulated macrophages and endothelia l cells of the microvessels. Furthermore, VEGF mRNA expression was det ected in atherosclerotic coronary segments but not in normal coronary segments. The immunostainings for flt-1 and Flk-1 were detected in agg regating macrophages in atherosclerotic lesions and also in endothelia l cells of the microvessels in totally occlusive lesions. Conclusions- These results demonstrate distinct expression of VEGF and its receptor s (flt-1 and Flk-1) in atherosclerotic lesions in human coronary arter ies. Considering the multipotent actions of VEGF documented experiment ally in vivo and in vitro, our findings suggest that VEGF may have som e role in the progression of human coronary atherosclerosis, as well a s in recanalization processes in obstructive coronary diseases.