Angiotensin II induces NF-κB activation in HUVEC via the p38MAPK pathway

Angiotensin II (Ang II) is the main active peptide of the renin-angiotensin system (RAS), producing a number of inflammatory mediators that lead to endothelial dysfunction and the progression of atherosclerosis. Ang II-induced NF-kappa B nuclear translocation plays a pivotal role in this response. This study examines the NF-kappa B activation mechanism elicited by Ang II in human umbilical vein endothelial cells (HUVEC). Electrophoretic mobility shift assays and Western blotting revealed that Ang II, signaling via AT,, produces a time-dependent increase in NF-kappa B DNA binding and I kappa B alpha degradation. These results also demonstrate that Ang II leads to MAPK phosphorylation and p38MAPK pathway-induced NF-kappa B activation. Furthermore, AT, is required for p38MAPK phosphorylation induced by Ang II. This study provides evidence that Ang II elicits NF-kappa B activation via the p38MAPK pathway in HUVEC. (c) 2006 Elsevier Inc. All rights reserved.