Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

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

Authors: Yet, SF  Layne, MD  Liu, X  Chen, YH  Ith, B  Sibinga, NE  Perrella, MA 
Citation: Yet SF, etal., FASEB J. 2003 Sep;17(12):1759-61. Epub 2003 Jul 3.
Pubmed: (View Article at PubMed) PMID:12958201
DOI: Full-text: DOI:10.1096/fj.03-0187fje

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.


Disease Annotations
Objects Annotated

Additional Information

RGD Object Information
RGD ID: 1598395
Created: 2006-11-26
Species: All species
Last Modified: 2006-11-26
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.