Femoral Artery Neointimal Hyperplasia is Reduced After Wire Injury in Ref-1+/- Mice.
From: Lillehei Heart Institute, Univ. of Minnesota, 420 Delaware St., Minneapolis, MN 55455, USA. jlhall@umn.edu
American journal of physiology. Heart and circulatory physiology
- Publish Date: Jan 2007
- ISSN: 0363-6135
- Volume: 292
- Issue: 1
- Pages: H516-21
- Medium: Print
- Language: English
- Citation (JAMA): Basi David L, Adhikari Neeta, Mariash Ami, et al. Femoral Artery Neointimal Hyperplasia is Reduced After Wire Injury in Ref-1+/- Mice.. Am. J. Physiol. Heart Circ. Physiol. Jan 2007;292:H516-21
Abstract
Redox factor-1 (Ref-1) is a multifunctional protein that regulates redox, DNA repair, and the response to cell stress. We previously demonstrated that Ref-1(+/-) mice exhibit a significantly reduced Ref-1 mRNA and protein levels within the vasculature, which are associated with increased oxidative stress. The goal of this study was to test the hypothesis that partial loss of Ref-1 altered the cellular response to vascular injury. Fourteen days after femoral artery wire injury, we found that vessel intima-to-media ratio was significantly reduced in Ref-1(+/-) mice compared with that in wild-type mice (P < 0.01). Bromodeoxyuridine labeling and transferase-mediated dUTP nick-end labeling staining at 14 days did not differ in the Ref-1(+/-) mice. In vitro studies found no significant changes in either serum-induced proliferation or baseline apoptosis in Ref-1(+/-) vascular smooth muscle cells. Exposure to Fas ligand; however, did result in increased susceptibility of Ref-1(+/-) vascular smooth muscle cells to apoptosis (P < 0.001). Ref-1(+/-) mice exhibited an increase in circulating baseline levels of IL-10, IL-1alpha, and VEGF compared with those in wild-type mice but a marked impairment in these pathways in response to injury. In sum, loss of a single allele of Ref-1 is sufficient to reduce intimal lesion formation and to alter circulating cytokine and growth factor expression.
Mesh Headings (Keywords): Animals, Apoptosis, Cell Proliferation, DNA-(Apurinic or Apyrimidinic Site) Lyase, Femoral Artery, Hyperplasia, Mice, Mice, Knockout, Tunica Intima
Check for Full Text / PubMed Unique Identifier (PMID): 16936011
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