Heme oxygenase-1 increases endothelial progenitor cells.
OBJECTIVE
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.


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.
Wu
Ben J
BJ
Centre for Vascular Research, School of Medical Sciences and Bosch Institute, Faculty of Medicine, University of Sydney, NSW 2006, Australia.
Midwinter
Robyn G
RG
Cassano
Carlos
C
Beck
Konstanze
K
Wang
Yutang
Y
Changsiri
Dechaboon
D
Gamble
Jennifer R
JR
Stocker
Roland
R
D000818:Animals; D000950:Antigens, Ly / Q000502:physiology; D002248:Carbon Monoxide / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology*; D004790:Enzyme Induction / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D051547:Heme Oxygenase-1 / Q000502:physiology*; D006965:Hyperplasia; D008565:Membrane Proteins / Q000502:physiology; D051379:Mice; D011341:Probucol / Q000031:analogs & derivatives / Q000494:pharmacology; D011817:Rabbits; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000502:physiology
D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D002248:Carbon Monoxide; D051547:Heme Oxygenase-1; D040301:Vascular Endothelial Growth Factor Receptor-2; C471047:succinobucol; D011341:Probucol