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Aim Premature senescence of the vascular endothelial cells is a leading cause of endothelial dysfunction.Our previous observations suggest that upregulation of heme oxygenase1 (HO1) improves endothelial function by attenuating endotheliumdependent contractions and potentiating endotheliumdependent hyperpolarization.The present study aimed to investigate the effect of HO1 on endothelial senescence and the underlying mechanisms.Methods Human umbilical vein endothelial ceils (HUVEC) were treated with 50 μmol · L1 H2O2 to induce premature senescence.HO1 was upregulated by the pharmacological inducer hemin, whereas it was knocked down by RNA silencing.Results H2O2 remarkably induced HUVEC senescence as detecting by the immunostaining of senescenceassociated 3galactosidase.Overexpression of HO1 by hemin reversed H2O2induced senescence in a dosedependent manner.Silencing of HO1 triggered HUVEC senescence, even in the absence of H2O2.In addition, HO1 induction prevented the decrease of eNOS phosphorylation at Serine 1177 stimulated by H2O2.Contrarily, HO1 silencing impaired eNOS phosphorylation.The total protein expression of eNOS was not altered by HO1.Further, coimmunoprecipitation experiments showed that HO1 directly interacted with eNOS.Conclusions HO1 ameliorated endothelial senescence probably through interacting with eNOS and affecting its phosphorylation modification.