Nature Medicine
7, 693 - 698 (2001)
doi:10.1038/89068
Heme oxygenase-1 protects against vascular constriction and proliferationHenricus J. Duckers1, Manfred Boehm1, Andrea L. True1, Shaw-Fang Yet4, Hong San1, James L. Park3, R. Clinton Webb3, Mu-En Lee4, Gary J. Nabel2
& Elizabeth G. Nabel11
Vascular Biology Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA
2
Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, USA
3
Department of Physiology, Medical College of Georgia, Augusta, Georgia, USA
4
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
Correspondence should be addressed to Elizabeth G. Nabel enabel@nih.govHeme oxygenase (HO-1, encoded by Hmox1) is an inducible protein activated in systemic inflammatory conditions by oxidant stress. Vascular injury is characterized by a local reparative process with inflammatory components, indicating a potential protective role for HO-1 in arterial wound repair. Here we report that HO-1 directly reduces vasoconstriction and inhibits cell proliferation during vascular injury. Expression of HO-1 in arteries stimulated vascular relaxation, mediated by guanylate cyclase and cGMP, independent of nitric oxide. The unexpected effects of HO-1 on vascular smooth muscle cell growth were mediated by cell-cycle arrest involving p21Cip1. HO-1 reduced the proliferative response to vascular injury in vivo; expression of HO-1 in pig arteries inhibited lesion formation and Hmox1
-/- mice produced hyperplastic arteries compared with controls. Induction of the HO-1 pathway moderates the severity of vascular injury by at least two adaptive mechanisms independent of nitric oxide, and is a potential therapeutic target for diseases of the vasculature.
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