Heme oxygenase-1 ameliorates endothelial senescence via eNOS

Aim Premature senescence of the vascular endothelial cells is a leading cause of endothelial dysfunc- tion. Our previous observations suggest that up-regulation of heme oxygenase-1 （HO-1） improves endothelial func- tion by attenuating endothelium-dependent contractions and potentiating endothelium-dependent hyperpolarization. The present study aimed to investigate the effect of HO-1 on endothelial senescence and the underlying mecha- nisms. Methods Human umbilical vein endothelial cells （HUVEC） were treated with 50 μmol · L^-1 H2 02 to in- duce premature senescence. HO-1 was up-regulated by the pharmacological inducer hemin, whereas it was knocked down by 1RNA silencing. Results H2 02 remarkably induced HUVEC senescence as detecting by the immunostain- ing of senescence-associated β-galactosidase. Overexpression of HO-1 by hemin reversed H2 02 -induced senescence in a dose-dependent manner. Silencing of HO-1 triggered HUVEC senescence, even in the absence of H202. In addition, HO-1 induction prevented the decrease of eNOS phosphorylation at Serine 1177 stimulated by H202. Contrarily, HO-1 silencing impaired eNOS phosphorylation. The total protein expression of eNOS was not altered by HO-1. Further, co-immunoprecipitation experiments showed that HO-1 directly interacted with eNOS. Conclusions HO-1 ameliorated endothelial senescence probably through interacting with eNOS and affecting its phosphoryla- tion modification.