Prevention of aortic fibrosis by N-acetyl-seryl-aspartyllysyl-proline in angiotensin II-induced hypertension

Physiol 295: H1253–H1261, 2008. First published July 18, 2008; doi:10.1152/ajpheart.00481.2008.—Fibrosis is an important component of large conduit artery disease in hypertension. The endogenous tetrapep-tide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) has anti-inflamma-tory and antifibrotic effects in the heart and kidney. However, it is not known whether Ac-SDKP has an anti-inflammatory and antifibrotic effect on conduit arteries such as the aorta. We hypothesize that in ANG II-induced hypertension Ac-SDKP prevents aortic fibrosis and that this effect is associated with decreased protein kinase C (PKC) activation, leading to reduced oxidative stress and inflammation and a decrease in the profibrotic cytokine transforming growth factor-1 (TGF-1) and phosphorylation of its second messenger Smad2. To test this hypothesis we used rats with ANG II-induced hyperten-sion and treated them with either vehicle or Ac-SDKP. In this hypertensive model we found an increased collagen deposition an