Heme Oxygenase-1 Increases Endothelial Progenitor Cells
- 1 October 2009
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Arteriosclerosis, Thrombosis, and Vascular Biology
- Vol. 29 (10), 1537-1542
- https://doi.org/10.1161/atvbaha.109.184713
Abstract
Objectives— Induction of heme oxygenase-1 (HO-1) protects against atherosclerotic disease in part by promoting reendothelialization. As endothelial progenitor cells (EPCs) contribute to reendothelialization, we examined the role of HO-1 on bone marrow and circulating EPCs. Methods and Results— In a rabbit model of aortic balloon injury, pharmacological induction of HO-1 enhanced reendothelialization at sites with and without adjacent blood vessels, the latter indicative of a contribution by EPCs. Coinciding with maximal HO-1 induction in the injured vessel, plasma concentrations of bilirubin and the numbers of circulating progenitor cells were elevated. Both processes were abolished by cotreatment of the animals with an inhibitor of HO-1. Inducers of HO-1 promoted bone marrow cells to form progenitor cell colonies, and Flk1 + /Sca-1 + -cells to adhere to the luminal surface of the injured vessel. In noninjured mice, HO-1 inducers also increased bone marrow and circulating EPCs, and the ability of these cells to differentiate and form colonies. Compared to wild-type mice, bone marrow cells from HO-1 −/− mice generated fewer endothelial colony-forming cells, and HO-1 inducers failed to promote CFU-Hill colony formation. Conclusions— These findings suggest that HO-1 contributes to vascular repair by increasing circulating EPCs derived from the bone marrow.Keywords
This publication has 43 references indexed in Scilit:
- Heme Oxygenase-1Circulation, 2006
- Antioxidants protect from atherosclerosis by a heme oxygenase-1 pathway that is independent of free radical scavengingThe Journal of Experimental Medicine, 2006
- Heme Oxygenase-1/Carbon Monoxide: From Basic Science to Therapeutic ApplicationsPhysiological Reviews, 2006
- Role of Oxidative Modifications in AtherosclerosisPhysiological Reviews, 2004
- Probucol Promotes Functional Reendothelialization in Balloon-Injured Rabbit AortasCirculation, 2003
- AGI-1067: A Multifunctional Phenolic Antioxidant, Lipid Modulator, Anti-Inflammatory and Antiatherosclerotic AgentThe Journal of pharmacology and experimental therapeutics, 2003
- Bone Marrow–Derived Progenitor Cells Modulate Vascular Reendothelialization and Neointimal FormationArteriosclerosis, Thrombosis, and Vascular Biology, 2002
- Heme oxygenase-1 protects against vascular constriction and proliferationNature Medicine, 2001
- Isolation of Putative Progenitor Endothelial Cells for AngiogenesisScience, 1997
- Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines.JCI Insight, 1995