Naslov
Apolipoprotein E Enhances Endothelial-NO Production by Modulating Caveolin 1 Interaction With Endothelial NO Synthase

Autori
Yue, Lili ; Bian, Jing-Tan ; Grizelj, Ivana ; Čavka, Ana ; Phillips, Shane A. ; Makino, Ayako ; Mazzone, Theodore

Izvornik
Hypertension (Dallas, Tex.) (0194-911X) 60 (2012), 4; 1040-1046

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
apolipoprotein E; endothelium; caveolin 1; macrophages; NO; NO synthase

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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