Nitrosation of CD36 Regulates Endothelial Function and Serum Lipids.

IF 7.4 1区 医学 Q1 HEMATOLOGY
Melissa A Luse, Wyatt J Schug, Luke S Dunaway, Shruthi Nyshadham, Skylar A Loeb, Alicia Carvalho, Rachel Tessema, Caitlin Pavelec, T C Stevenson Keller, Xiaohong Shu, Claire A Ruddiman, Anna Kosmach, Timothy M Sveeggen, Ray Mitchell, Pooneh Bagher, Richard D Minshall, Norbert Leitnger, Linda Columbus, Kandice R Levental, Ilya Levental, Miriam Cortese-Krott, Brant E Isakson
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Abstract

Background: During obesity, endothelial cells (ECs) become lipid laden, leading to endothelial dysfunction. We tested posttranslational modification on cluster of differentiation 36 (CD36) that may regulate EC lipid accumulation.

Methods: We used an EC-specific Cav1 (caveolin-1) knockout mouse, nitrosation and palmitoylation assays, and whole animal Nγ-nitro-l-arginine methyl ester administration to examine blood lipids.

Results: EC-specific Cav1 knockout male mice are hyperlipidemic regardless of diet but retain endothelial cell function. We found these mice have significantly increased NO in response to the lack of Cav1, and the presence or absence of NO toggled inversely EC lipid content and plasma lipid in mice. The NO nitrosated the fatty acid translocase CD36 at the same cysteines that are palmitoylated on CD36. The nitrosation of CD36 prevented its trafficking to the plasma membrane and decreased lipid accumulation. The physiological effect of this mechanism was a reliance on NO for endothelial function and not dilation.

Conclusions: This work suggests that CD36 nitrosation occurs as a protective mechanism to prevent EC lipotoxicity.

CD36亚硝化调节内皮功能和血脂。
背景:在肥胖期间,内皮细胞(ECs)成为脂质负载,导致内皮功能障碍。我们测试了CD36的翻译后修饰可能调节EC脂质积累。方法:采用ec特异性Cav1 (caveolin-1)敲除小鼠,亚硝化和棕榈酰化实验,以及全动物n- γ-硝基-l-精氨酸甲酯给药检测血脂。结果:ec特异性Cav1敲除的雄性小鼠无论饮食如何都是高脂血症,但保持内皮细胞功能。我们发现,这些小鼠在缺乏Cav1的情况下,NO显著增加,并且NO的存在或缺失与小鼠EC脂质含量和血浆脂质呈负相关。一氧化氮亚硝化脂肪酸转位酶CD36在与CD36棕榈酰化相同的半胱氨酸上。CD36的亚硝化作用阻止其转运到质膜,减少脂质积累。这种机制的生理作用是依赖于一氧化氮的内皮功能,而不是扩张。结论:本研究提示CD36亚硝化是一种预防EC脂毒性的保护机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
15.60
自引率
2.30%
发文量
337
审稿时长
2-4 weeks
期刊介绍: The journal "Arteriosclerosis, Thrombosis, and Vascular Biology" (ATVB) is a scientific publication that focuses on the fields of vascular biology, atherosclerosis, and thrombosis. It is a peer-reviewed journal that publishes original research articles, reviews, and other scholarly content related to these areas. The journal is published by the American Heart Association (AHA) and the American Stroke Association (ASA). The journal was published bi-monthly until January 1992, after which it transitioned to a monthly publication schedule. The journal is aimed at a professional audience, including academic cardiologists, vascular biologists, physiologists, pharmacologists and hematologists.
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