Heme oxygenase-1 protects against vascular constriction and proliferation
- PMID:11385506
- DOI: 10.1038/89068
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.
Comment in
- A protective player in the vascular response to injury.Schwartz SM.Schwartz SM.Nat Med. 2001 Jun;7(6):656-7. doi: 10.1038/89019.Nat Med. 2001.PMID:11385495No abstract available.
Similar articles
- Human heme oxygenase: cell cycle-dependent expression and DNA microarray identification of multiple gene responses after transduction of endothelial cells.Abraham NG, Scapagnini G, Kappas A.Abraham NG, et al.J Cell Biochem. 2003 Dec 15;90(6):1098-111. doi: 10.1002/jcb.10736.J Cell Biochem. 2003.PMID:14635185
- Vascular smooth muscle cell-directed overexpression of heme oxygenase-1 elevates blood pressure through attenuation of nitric oxide-induced vasodilation in mice.Imai T, Morita T, Shindo T, Nagai R, Yazaki Y, Kurihara H, Suematsu M, Katayama S.Imai T, et al.Circ Res. 2001 Jul 6;89(1):55-62. doi: 10.1161/hh1301.092679.Circ Res. 2001.PMID:11440978
- Hemin inhibits hypertensive rat vascular smooth muscle cell proliferation through regulation of cyclin D and p21.Jeon EM, Choi HC, Lee KY, Chang KC, Kang YJ.Jeon EM, et al.Arch Pharm Res. 2009 Mar;32(3):375-82. doi: 10.1007/s12272-009-1310-2. Epub 2009 Apr 23.Arch Pharm Res. 2009.PMID:19387581
- Heme oxygenase--carbon monoxide signalling pathway as a physiological regulator of vascular smooth muscle cells.Christova T, Diankova Z, Setchenska M.Christova T, et al.Acta Physiol Pharmacol Bulg. 2000;25(1):9-17.Acta Physiol Pharmacol Bulg. 2000.PMID:11140191Review.
- [Heme oxygenase and carbon monoxide in the physiology and pathology of the cardiovascular system].Bełtowski J, Jamroz A, Borkowska E.Bełtowski J, et al.Postepy Hig Med Dosw (Online). 2004 Mar 3;58:83-99.Postepy Hig Med Dosw (Online). 2004.PMID:15069378Review.Polish.
Cited by
- Novel therapies for cyclic GMP control of vascular smooth muscle growth.Tulis DA.Tulis DA.Am J Ther. 2008 Nov-Dec;15(6):551-64. doi: 10.1097/MJT.0b013e318140052f.Am J Ther. 2008.PMID:19127140Free PMC article.Review.
- Patients with Gilbert syndrome and type 2 diabetes have lower prevalence of microvascular complications.Uribe-Weichers AC, Gómez-Pérez FJ, Lam-Chung CE, Cuevas-Ramos D.Uribe-Weichers AC, et al.Metabol Open. 2021 Jul 28;11:100114. doi: 10.1016/j.metop.2021.100114. eCollection 2021 Sep.Metabol Open. 2021.PMID:34386764Free PMC article.
- The apolipoprotein A-I mimetic peptide, D-4F, restrains neointimal formation through heme oxygenase-1 up-regulation.Liu D, Wu M, Du Q, Ding Z, Qian M, Tong Z, Xu W, Zhang L, Chang H, Wang Y, Huang C, Lin D.Liu D, et al.J Cell Mol Med. 2017 Dec;21(12):3810-3820. doi: 10.1111/jcmm.13290. Epub 2017 Aug 2.J Cell Mol Med. 2017.PMID:28767201Free PMC article.
- Cardioprotective Effect of Selective Estrogen Receptor Modulator Raloxifene Are Mediated by Heme Oxygenase in Estrogen-Deficient Rat.Posa A, Szabó R, Kupai K, Berkó AM, Veszelka M, Szűcs G, Börzsei D, Gyöngyösi M, Pávó I, Deim Z, Szilvássy Z, Juhász B, Varga C.Posa A, et al.Oxid Med Cell Longev. 2017;2017:2176749. doi: 10.1155/2017/2176749. Epub 2017 Jul 9.Oxid Med Cell Longev. 2017.PMID:28770019Free PMC article.
- Heme Oxygenase-1, a Key Enzyme for the Cytoprotective Actions of Halophenols by Upregulating Nrf2 Expression via Activating Erk1/2 and PI3K/Akt in EA.hy926 Cells.Feng XE, Liang TG, Gao J, Kong P, Ge R, Li QS.Feng XE, et al.Oxid Med Cell Longev. 2017;2017:7028478. doi: 10.1155/2017/7028478. Epub 2017 Jun 14.Oxid Med Cell Longev. 2017.PMID:28694915Free PMC article.
Publication types
MeSH terms
Substances
Related information
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases