Flavonoids have been suggested to protect against atherosclerosis via their antioxidant and anti-inflammatory properties. Heme oxygenase-1 (HO-1) is an enzyme that plays an important role in the vascular system, and its induction may provide a protective role against atherosclerosis. We hypothesize that flavonoids can down-regulate endothelial inflammatory parameters by modulating HO-1-regulated cell signaling. We focused on the role of HO-1 and its major metabolic product, bilirubin, on mechanisms of tumor necrosis factor-α-induced endothelial cell activation and protection by the catechin epigallocatechin gallate (EGCG). Pretreatment with EGCG inhibited the secretion of monocyte chemoattractant protein-1 and the activation of activator protein-1 in porcine aortic endothelial cells stimulated with tumor necrosis factor-α. Moreover, EGCG up-regulated the expression of HO-1 and further induced the secretion of bilirubin. The observed anti-inflammatory effects of EGCG were mimicked by the HO-1 inducer cobalt protoporphyrin and abolished by HO-1 gene silencing. These data suggest that the protective properties of flavonoids, such as EGCG, against endothelial inflammation may be regulated in part though induction of HO-1 and subsequent activator protein-1 signaling.
Copyright © 2010. Published by Elsevier Inc.