Absence of heme oxygenase‐1 exacerbates atherosclerotic lesion formation and vascular remodeling
Copyright policy )Absence of heme oxygenase‐1 exacerbates atherosclerotic lesion formation and vascular remodeling
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.
- Brigham and Women's Faulkner Hospital United States
- Yeshiva University United States
- Albert Einstein College of Medicine United States
- Kaohsiung Medical University Taiwan
Mice, Knockout, Cell Death, Arteriosclerosis, Graft Occlusion, Vascular, Calcinosis, Membrane Proteins, Models, Biological, Muscle, Smooth, Vascular, Mice, Oxidative Stress, Apolipoproteins E, Heme Oxygenase (Decyclizing), Animals, Heme Oxygenase-1
Mice, Knockout, Cell Death, Arteriosclerosis, Graft Occlusion, Vascular, Calcinosis, Membrane Proteins, Models, Biological, Muscle, Smooth, Vascular, Mice, Oxidative Stress, Apolipoproteins E, Heme Oxygenase (Decyclizing), Animals, Heme Oxygenase-1
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