Heme oxygenase-1 protects against vascular constriction and proliferation

Henricus J. Duckers, Manfred Boehm, Andrea L. True, Shaw Fang Yet, Hong San, James L. Park, R. Clinton Webb, Mu En Lee, Gary J. Nabel, Elizabeth G. Nabel

Research output: Contribution to journalArticle

431 Scopus citations

Abstract

Heme 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.

Original languageEnglish (US)
Pages (from-to)693-698
Number of pages6
JournalNature Medicine
Volume7
Issue number6
DOIs
StatePublished - Jul 9 2001

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Duckers, H. J., Boehm, M., True, A. L., Yet, S. F., San, H., Park, J. L., Clinton Webb, R., Lee, M. E., Nabel, G. J., & Nabel, E. G. (2001). Heme oxygenase-1 protects against vascular constriction and proliferation. Nature Medicine, 7(6), 693-698. https://doi.org/10.1038/89068