Gene transfer of human heme oxygenase into coronary endothelial cells potentially promotes angiogenesis.
Heme oxygenase (HO-1) is a stress protein that has been suggested to participate in defense mechanisms against agents that induce oxidative injury such as hemoglobin/heme, hypoxia-ischemia and cytokines. Overexpression of HO-1 in endothelial cells (EC) might, therefore, protect against oxidative stress produced under these pathological conditions, by generation of CO, a vasodilator, and bilirubin, which has antioxidant properties that enhance blood vessel formation to counteract hypoxia-induced injury. A plasmid containing the cytomegalovirus promoter (pCMV) neomycin human HO-1 gene complexed to cationic liposomes, lipofectin, was used to transfect rabbit coronary microvessel EC. Cells transfected with human HO-1 gene demonstrated a twofold increase in HO activity and maintained a similar phenotype as in the nontransfected cells. Cell number in transfected cells with human HO-1 gene increased by about 45%, as compared to nontransfected or those transfected with control pCMV. Transfected and nontransfected EC revealed a similar response to basic fibroblast growth factor (bFGF) in capillary formation. However, transfected cells with the human HO-1 gene exhibited a twofold increase in blood vessel formation. The angiogenic response of EC to overexpression of HO-1 gene provides direct evidence that the inductive form of HO-1 following injury represents an important tissue adaptive mechanism for moderating the severity of cell damage produced in inflammatory reaction sites of hemorrhage, thrombosis and hypoxic-ischemia. Thus, HO-1 may participate in the regulation of EC activation, proliferation and angiogenesis.
Deramaudt
B M
BM
Department of Pharmacology, New York Medical College, Valhalla 10595, USA.
Braunstein
S
S
Remy
P
P
Abraham
N G
NG
D000818:Animals; D001483:Base Sequence; D001663:Bilirubin / Q000378:metabolism; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D004727:Endothelium / Q000098:blood supply*; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D018014:Gene Transfer Techniques; D006418:Heme / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D011817:Rabbits; D014162:Transfection
D016222:Fibroblast Growth Factor 2; D006418:Heme; D006419:Heme Oxygenase (Decyclizing); D001663:Bilirubin