Absence of heme oxygenase-1 exacerbates atherosclerotic lesion formation and vascular remodeling.

Shaw Fang Yet, Matthew D. Layne, Xiaoli Liu, Yen Hsu Chen, Bonna Ith, Nicholas E.S. Sibinga, Mark A. Perrella

Research output: Contribution to journalArticle

235 Scopus citations

Abstract

To examine the role of heme oxygenase (HO)-1 in the pathophysiology of vascular diseases, we generated mice deficient in both HO-1 and apolipoprotein E (HO-1-/-apoE-/-). Despite similar total plasma cholesterol levels in response to hypercholesterolemia, HO-1-/-apoE-/- mice, in comparison with HO-1+/+apoE-/- mice, had an accelerated and more advanced atherosclerotic lesion formation. In addition to greater lipid accumulation, these advanced lesions from HO-1-/-apoE-/- mice contained macrophages and smooth muscle alpha-actin-positive cells. We further tested the role of HO-1 on neointimal formation in a mouse model of vein graft stenosis. Autologous vein grafts in HO-1-/- mice showed robust neointima consisting of alpha-actin-positive vascular smooth muscle cells (VSMC) 10 days after surgery in comparison to the smaller neointima formed in autologous vein grafts in HO-1+/+ mice. However, at 14 days after surgery, the neointima from composite vessels of HO-1-/- mice was composed mainly of acellular material, indicative of substantial VSMC death. VSMC isolated from HO-1-/- mice were susceptible to oxidant stress, leading to cell death. Our data demonstrate that HO-1 plays an essential protective role in the pathophysiology of atherosclerosis and vein graft stenosis.

Original languageEnglish (US)
Pages (from-to)1759-1761
Number of pages3
JournalThe FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume17
Issue number12
DOIs
StatePublished - Sep 2003

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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