Gene transfer of human heme oxygenase into coronary endothelial cells potentially promotes angiogenesis

Publisher Website
Google Scholar
Abstract
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. J. Cell. Biochem. 68:121–127, 1998.

This publication has 29 references indexed in Scilit: