EDN1 and atherosclerosis: ET-1 stimulates pro-oncogene expressions of c-myc and c-fos and DNA synthesis in vascular smooth muscle cells in a dose-dependent manner through strong and long-lasting vasoconstrictor effects, thereby promoting the proliferation of VSMCs and participating in the formation of atherosclerosis.16 With the co-culture of endothelial cells and VSMCs, Morita et al.6 found that HO-1 mRNA expression was increased in hypoxic VSMCs, and that hypoxic VSMCs could inhibit the high expression of ET-1 and PDGF-B mRNA and the secretion of ET-1 in hypoxia-induced human umbilical vein endothelial cells.