GENE-TRANSFER OF HUMAN HEME OXYGENASE INTO CORONARY ENDOTHELIAL-CELLSPOTENTIALLY PROMOTES ANGIOGENESIS

Heme oxygenase (HO-1) is a stress protein that has been suggested to p articipate in defense mechanisms against agents that induce oxidative injury such as hemoglobin/heme, hypoxia-ischemia and cytokines. Overex pression of HO-1 in endothelial cells (EC) might, therefore, protect a gainst oxidative stress produced under these pathological conditions, by generation of CO, a vasodilator and bilirubin, which has antioxidan t properties that enhance blood vessel formation to counteract hypoxia -induced injury. A plasmid containing the cytomegalovirus promoter (pC MV) neomycin human HO-1 gene complexed to cationic liposomes, lipofect in, was used to transfect rabbit coronary microvessel EC. Cells transf ected with human HO-1 gene demonstrated a twofold increase in HO activ ity and maintained a similar phenotype as in the nontransfected cells. Cell number in transfected cells with human HO-1 gene increased by ab out 45%, as compared to nontransfected or those transfected with contr ol pCMV. Transfected and nontransfected EC revealed a similar response to basic fibroblast growth factor (bFCF) in capillary formation. Howe ver, transfected cells with the human HO-1 gene exhibited a twofold in crease in blood vessel formation. The angiogenic response of EC to ove rexpression of HO-1 gene provides direct evidence that the inductive f orm of HO-1 following injury represents an important tissue adaptive m echanism for moderating the severity of cell damage produced in inflam matory reaction sites of hemorrhage, thrombosis and hypoxic-ischemia. Thus, HO-1 may participate In the regulation of EC activation, prolife ration and angiogenesis. (C) 1998 Wiley-Liss, Inc.