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

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

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

The FASEB Journal express article10.1096/fj.03-0187fje. Published online July 3, 2003. 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, § and Mark A. Perrella* *Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women?s Hospital, Boston, MA; ? Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; § Cardiovascular Division, Department of Medicine, Albert Einstein College of Medicine, Bronx, NY Corresponding author: Shaw-Fang Yet, Pulmonary and Critical Care Division, Brigham and Women?s Hospital, 75 Francis Street, Thorn 1333, Boston, MA 02115. E-mail: syet@rics.bwh.harvard.edu 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 α-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 α-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 dea

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