ROS-dependent Syk and Pyk2-mediated STAT1 Activation is Required for 15(S)-hydroxyeicosatetraenoic Acid-induced CD36 Expression and Foam Cell Formation

Overview

Journal Free Radic Biol Med

Specialties Biochemistry
Biology
General Medicine

Date 2014 Aug 26

PMID 25152235

Citations 20

Authors

Sivareddy Kotla

Nikhlesh K Singh

James G Traylor Jr

A Wayne Orr

Gadiparthi N Rao

Affiliations

Soon will be listed here.

Abstract

15(S)-Hydroxyeicosatetraenoic acid (15(S)-HETE), the major 15-lipoxygenase 1/2 (15-LO1/2) metabolite of arachidonic acid (AA), induces CD36 expression through 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 Western 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 with increased lipid deposits, macrophage content, and lesion progression in the aortic roots. Human atherosclerotic arteries also showed increased 15-LO1 expression, STAT1 phosphorylation, and CD36 levels as compared to normal arteries. Together, these findings suggest that 12/15-LO metabolites of AA, particularly 12/15(S)-HETE, might play a crucial role in atherogenesis by enhancing foam cell formation.

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