All ETDs from UAB

Advisory Committee Chair

Anupam Agarwal

Advisory Committee Members

Shannon M Bailey

John C Chatham

James F George

Aimee Landar

Rosa A Serra

Document Type

Thesis

Date of Award

2012

Degree Name by School

Master of Science in Biomedical Science (MSBMS) School of Engineering

Abstract

INVESTIGATING POTENTIAL NOVEL ANGIOGENIC AND IMMUNOGENIC PROPERTIES OF HEME OXYGENASE-1 According to the American Heart Association and Centers of Disease Control and Prevention, cardiovascular diseases comprise the primary causes of death in the United States. Heme oxygenase-1 (HO-1), an inducible microsomal enzyme, catalyzes the rate limiting step in heme degradation releasing equimolar amounts of biliverdin, iron and carbon monoxide. Importantly, the induction of HO-1 is an adaptive response that affords protection in these disease states and several others. Expression of HO-1 has been demonstrated in several disease states and pathophysiological processes, including ischemia-reperfusion, inflammation and organ transplantation. This protection is due not only to the degradation of the pro-oxidant heme but can also be attributed to byproducts of the heme oxygenase reaction. The reaction products liberated by HO-1, including carbon monoxide (CO) and bilirubin, exert anti-oxidant, anti-inflammatory and anti-apoptotic effects. In addition to these well appreciated functions of HO-1, our laboratory has reported a novel role for HO-1 in stromal derived factor-1 (SDF-1) mediated angiogenesis. SDF-1 induced HO-1 in endothelial cells through a PKC-æ-dependent and VEGF-independent mechanism. SDF-1 and its receptors CXCR-4/7 play a major role in migration, recruitment and retention of endothelial progenitor cells (EPC) to sites of ischemic injury and contribute to neovascularization. Furthermore, HO-1 plays a role in the immune response. We have shown that the absence of HO-1 strongly affects differentiation of resident dendritic cell (DC) subsets in vivo and abrogates regulatory T cell mediated suppression of T cell activation by DC in vitro. These findings support the concept that modulation of the immune response, and therefore allograft rejection, is through the effect of HO-1 on the differentiation and function of DCs. While these preliminary studies provided important early insights, several key questions have emerged that remain unanswered. Future investigations into this research area could demonstrate a novel mechanistic role for HO-1 in mediating angiogenic and immunogenic response, which would provide new avenues for therapeutic approaches in vascular repair and organ transplantation.

Included in

Engineering Commons

Share

COinS