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

doi:10.1038/89068

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

Physiology

Research output: Contribution to journal › Article › peer-review

465 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 p21^Cip1. 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 language	English (US)
Pages (from-to)	693-698
Number of pages	6
Journal	Nature Medicine
Volume	7
Issue number	6
DOIs	https://doi.org/10.1038/89068
State	Published - 2001

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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@article{3003b6d85eb34265a1f4ecb2e3e360fe,

title = "Heme oxygenase-1 protects against vascular constriction and proliferation",

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.",

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

note = "Funding Information: Acknowledgments H.J.D. was supported by a grant from NATO (NWO) and the Intercardiologisch Instituut Nederland (ICIN).",

year = "2001",

doi = "10.1038/89068",

language = "English (US)",

volume = "7",

pages = "693--698",

journal = "Nature Medicine",

issn = "1078-8956",

publisher = "Nature Publishing Group",

number = "6",

}

TY - JOUR

T1 - Heme oxygenase-1 protects against vascular constriction and proliferation

AU - Duckers, Henricus J.

AU - Boehm, Manfred

AU - True, Andrea L.

AU - Yet, Shaw Fang

AU - San, Hong

AU - Park, James L.

AU - Clinton Webb, R.

AU - Lee, Mu En

AU - Nabel, Gary J.

AU - Nabel, Elizabeth G.

N1 - Funding Information: Acknowledgments H.J.D. was supported by a grant from NATO (NWO) and the Intercardiologisch Instituut Nederland (ICIN).

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

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DO - 10.1038/89068

M3 - Article

C2 - 11385506

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VL - 7

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EP - 698

JO - Nature Medicine

JF - Nature Medicine

IS - 6

ER -

Heme oxygenase-1 protects against vascular constriction and proliferation

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