Redox Factor-1 Activates Endothelial SIRTUIN1 through Reduction of Conserved Cysteine Sulfhydryls in Its Deacetylase Domain
Figure 5
SIRT1 rescues impaired endothelium-dependent vasorelaxation in APE1/Ref-1 heterozygous mice.
(A) Adenoviral gene transfer of SIRT1 increases vascular SIRT1 activity. Wild-type SIRT1 was overexpressed ex vivo in aortic sections of APE1/Ref-1+/− mice using AdSIRT1. AdLacZ was used as control. SIRT1 protein and activity in whole aortas was determined. * P<0.05, (n = 3) (B) Overexpression of SIRT1 restores endothelium-dependent vasorelaxation in APE1/Ref-1+/− mice. Wild-type SIRT1 was overexpressed ex vivo in aortic sections of APE1/Ref-1+/− mice using AdSIRT1. AdLacZ was used as control. Acetylcholine-induced endothelium-dependent vasorelaxation was measured in aortic sections of APE1/Ref-1+/+ mice (♦), APE1/Ref-1+/− mice infected with AdSIRT1 (▪), and APE1/Ref-1+/− mice infected with AdLacZ (▴).* P<0.01 compared with APE1/Ref-1+/+ and APE1/Ref-1+/−+AdSIRT1 (n = 6). (C) Bioavailable NO in aortic sections of APE1/Ref-1+/+ mice (♦), APE1/Ref-1+/− mice infected with AdSIRT1 (▪), and APE1/Ref-1+/− mice infected with AdLacZ (▴).*P<0.01 compared with APE1/Ref-1+/+ mice and APE1/Ref-1+/− mice+AdSIRT1 (n = 5). (D) Sodium nitroprusside (SNP)-induced endothelium-independent vasorelaxation in aortic sections of APE1/Ref-1+/+ mice (♦), APE1/Ref-1+/− mice infected with AdSIRT1 (▪), and APE1/Ref-1+/− mice infected with AdLacZ (▴) (n = 4).