Abstract 674: 15(S)-Hydroxyeicosatetraenoic Acid Induces Foam Cell Formation by Enhancing CD36 Expression via Activation of ROS-Syk-Pyk2-STAT1 Signaling
15(S)-Hydroxyeicosatetraenoic acid (15(S)-HETE), the major 15-lipoxygenase 1 (15-LO1) metabolite of arachidonic acid (AA), induces CD36 expression in xanthine oxidase and NADPH oxidase-dependent ROS production and Syk and Pyk2-dependent STAT1 activation. In line with these observations, 15(S)-HETE also induced foam cell formation involving ROS, Syk, Pyk2 and STAT1-mediated CD36 expression. In addition, peritoneal macrophages from high-fat diet-fed ApoE-/- mice exhibited elevated levels of xanthine oxidase and NADPH oxidase activities, ROS production, Syk, Pyk2, and STAT1 phosphorylation and CD36 expression compared to those from ApoE-/-:12/15-LO-/- mice and these events correlated well with increased lipid deposits and macrophage content in the aortic arches resulting in atherosclerotic plaque formation. These findings strongly suggest that 12/15-LO metabolites of AA such as 15(S)-HETE play a crucial role in atherogenesis by enhancing foam cell formation.
Author Disclosures: S. Kotla: None. N.K. Singh: None. G.N. Rao: None.
- © 2014 by American Heart Association, Inc.