Femoral artery neointimal hyperplasia is reduced after wire injury in Ref-1+/- mice.
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.
Basi
David L
DL
Lillehei Heart Institute, Univ. of Minnesota, 420 Delaware St., Minneapolis, MN 55455, USA. jlhall@umn.edu
Adhikari
Neeta
N
Mariash
Ami
A
Li
Qinglu
Q
Kao
Esther
E
Mullegama
Sureni V
SV
Hall
Jennifer L
JL
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D049109:Cell Proliferation; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000276:immunology*; D005263:Femoral Artery / Q000276:immunology* / Q000293:injuries* / Q000473:pathology; D006965:Hyperplasia / Q000276:immunology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D017539:Tunica Intima / Q000276:immunology* / Q000293:injuries / Q000473:pathology*
C486216:Apex1 protein, mouse; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase