Angiogenesis and its regulation: Roles of vascular endothelial cell growthfactor

Neovascularization is well known to occur in human atherosclerotic plaques, proliferative retinopathies, and malignant neoplasias. However, its pathop hysiologic roles and mechanisms still remain unclear. In this study, histoc hemical examination of atherosclerotic plaques showed that vascular endothe lial cell growth factor (VEGF) was expressed by the smooth muscle cells and foamy macrophages in the atherosclerotic intimas. The number of VEGF-posit ive cells was positively correlated with the number of intimal blood vessel s. Moreover, VEGF gene transfer into rabbit carotid arteries using the heam agglutinating virus of Japan (HVJ)-liposomes showed that VEGF overexpressio n could induce the angiomatoid proliferation. In diabetic rats, VEGF was ov erexpressed in diabetic retinas, and thus the local overexpression of VEGF seemed to play an important role in the development of blood-retinal barrie r breakdown in simple diabetic retinopathy. These results indicated that th e VEGF can act as a local and endogenous regulator of endothelial cell func tions and that VEGF induces the neovascularization under pathopysiologic co nditions. On the other hand, the transfer of a decoy for the cis-element in the promoter region of the angiogenic factors would be an effective method for regulating angiogenesis, because other angiogenic factors' expression promoted by such cis-element could be simultaneously suppressed. Therefore, this method may supply a useful therapeutic tool for the regulation of pat hologic angiogenesis.