Bradykinin Protects Against Oxidative Stress-Induced Endothelial Cell Senescence

Hisko Oeseburg*, Dilek Iusuf, Pim van der Harst, Wiek H. van Gilst, Robert H. Henning, Anton J. M. Roks

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

70 Citaten (Scopus)

Samenvatting

Premature aging (senescence) of endothelial cells might play an important role in the development and progression of hypertension and atherosclerosis. We hypothesized that bradykinin, a hormone that mediates vasoprotective effects of angiotensin-converting enzyme inhibitors, protects endothelial cells from oxidative stress-induced senescence. Bradykinin treatment (0.001 to 1 nmol/L) dose-dependently decreased senescence induced by 25 mu mol/L of H2O2 in cultured bovine aortic endothelial cells, as witnessed by a complete inhibition of increased senescent cell numbers and a 34% reduction of the levels of the senescence-associated cell cycle protein p21. Because H2O2 induces senescence through superoxide-induced DNA damage, single-cell DNA damage was measured by comet assay. Bradykinin reduced DNA damage to control levels. The protective effect of bradykinin also resulted in a significant increase in the migration of H2O2-treated bovine aorta endothelial cells in an in vitro endothelial injury model, or "scratch" assay. The protective effect of bradykinin was abolished by the bradykinin B2 receptor antagonist HOE-140 and the NO production inhibitor N-omega-methyl-L-arginine acetate salt. Therefore, we conclude that bradykinin protects endothelial cells from superoxide-induced senescence through bradykinin B2 receptor-and NO-mediated inhibition of DNA damage. (Hypertension. 2009; 53[part 2]: 417-422.)

Originele taal-2English
Pagina's (van-tot)417-422
Aantal pagina's6
TijdschriftHypertension
Volume53
Nummer van het tijdschrift2
DOI's
StatusPublished - feb-2009
Evenement62nd Annual Fall Conference and Scientific Sessions of the American-Heart-Association-Council-for-High-Blood-Pressure-Research - , Gabon
Duur: 17-sep-200820-sep-2008

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