Apolipoprotein e enhances endothelial-NO production by modulating caveolin 1 interaction with endothelial no synthase

32Citations
Citations of this article
36Readers
Mendeley users who have this article in their library.

Abstract

Apolipoprotein E (apoE) is widely expressed in mammalian tissues, and one of the important tissue-specific effects is the atheroprotection ascribed to macrophage-derived apoE in the arterial wall. However, underlying mechanisms are not well understood. In this study, using subcellular fractionation, confocal microscopy, and coimmunoprecipitation, we demonstrated that macrophage-derived apoE is internalized by endothelial cells and impacts the subcellular distribution/interaction of caveolin 1 (cav-1) and endothelial NO synthase (eNOS). The addition of apoE disrupts the heteromeric complex formed between cav-1 and eNOS, and increases NO production. Sterol and oxysterol enhance endothelial cav-1/eNOS interaction and suppress NO production, but these effects are reversed by apoE. Silencing endothelial cav-1 attenuates apoE-induced NO production, establishing the importance of the cav-1-eNOS interaction for the increment in endothelial NO produced by apoE. Consistent with these observations, macrophage-derived apoE significantly improves vasodilation to acetylcholine in resistance arteries isolated from adipose tissue of obese humans. We conclude that macrophage-derived apoE enhances endothelial NO production by disrupting the inhibitory interaction of eNOS with cav-1. These results establish a novel mechanism by which apoE modulates endothelial cell function. © 2012 American Heart Association, Inc.

Cite

CITATION STYLE

APA

Yue, L., Bian, J. T., Grizelj, I., Cavka, A., Phillips, S. A., Makino, A., & Mazzone, T. (2012). Apolipoprotein e enhances endothelial-NO production by modulating caveolin 1 interaction with endothelial no synthase. Hypertension, 60(4), 1040–1046. https://doi.org/10.1161/HYPERTENSIONAHA.112.196667

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free