Advisor(s)
Anupam Agarwal
Committee Member(s)
Shannon M Bailey
John C Chatham
James F George
Aimee Landar
Rosa A Serra
Document Type
Thesis
Date of Award
2012
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.
ProQuest Publication Number
ISBN
978-1-267-41458-8
Recommended Citation
Frizell, Carl Antonio, "Investigating Potential Novel Angiogenic and Immunogenic Properties of Heme Oxygenase-1" (2012). All ETDs from UAB. 1672.
https://digitalcommons.library.uab.edu/etd-collection/1672
Comments
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