Journal
FASEB JOURNAL
Volume 17, Issue 10, Pages 1759-+Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.03-0187fje
Keywords
atherosclerosis; vein graft; pressure overload; oxidative stress
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To examine the role of hemeoxygenase(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.
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