Oxidized cholesteryl esters and inflammation.
Oxidized cholesteryl esters and inflammation.
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DOI：
10.1016/j.bbalip.2016.06.020
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发表时间：
2017-04
期刊：
影响因子：
--
通讯作者：
Miller YI
中科院分区：
文献类型：
--
作者：
Choi SH;Sviridov D;Miller YI
动脉粥样硬化的氧化假说认为，氧化LDL是动脉粥样硬化发展的主要致病因素。虽然这一假设得到了强有力的机制支持，许多动物研究表明，抗氧化剂，减少LDL氧化的动脉粥样硬化保护作用，抗氧化剂的人体临床试验的结果主要是负面的，除了在选定的患者组明显增加全身氧化应激。我们认为，即使降低人体脂蛋白氧化可能难以实现，但深入了解氧化LDL促进动脉粥样硬化的机制并靶向这些特定机制将为心血管疾病的治疗提供新的方法。在这篇综述文章中，我们专注于氧化胆固醇酯（OxCE），这是最低限度和广泛氧化LDL和人类动脉粥样硬化病变的主要组成部分。OxCE和OxCE-蛋白质共价加合物诱导深刻的生物学效应。在这些作用中，OxCE通过Toll样受体-4（TLR 4）和脾酪氨酸激酶激活巨噬细胞，并诱导巨胞饮，导致脂质积聚、活性氧的产生和炎性细胞因子的分泌。特异性抑制OxCE诱导的TLR 4活化，以及阻断OxCE的其他炎症作用，可能为动脉粥样硬化和心血管疾病提供新的治疗方法。
The oxidation hypothesis of atherosclerosis proposes that oxidized LDL is a major causative factor in the development of atherosclerosis. Although this hypothesis has received strong mechanistic support and many animal studies demonstrated profound atheroprotective effects of antioxidants, which reduce LDL oxidation, the results of human clinical trials with antioxidants were mainly negative, except in selected groups of patients with clearly increased systemic oxidative stress. We propose that even if reducing lipoprotein oxidation in humans might be difficult to achieve, deeper understanding of mechanisms by which oxidized LDL promotes atherosclerosis and targeting these specific mechanisms will offer novel approaches to treatment of cardiovascular disease. In this review article, we focus on oxidized cholesteryl esters (OxCE), which are a major component of minimally and extensively oxidized LDL and of human atherosclerotic lesions. OxCE and OxCE-protein covalent adducts induce profound biological effects. Among these effects, OxCE activate macrophages via toll-like receptor-4 (TLR4) and spleen tyrosine kinase and induce macropinocytosis resulting in lipid accumulation, generation of reactive oxygen species and secretion of inflammatory cytokines. Specific inhibition of OxCE-induced TLR4 activation, as well as blocking other inflammatory effects of OxCE, may offer novel treatments of atherosclerosis and cardiovascular disease.
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影响因子：
3.7
作者：
Choi SH;Wiesner P;Almazan F;Kim J;Miller YI
通讯作者：
Miller YI
DOI：
10.1161/01.atv.0000012782.59850.41
发表时间：
2002-04-01
影响因子：
8.7
作者：
Huber, J;Boechzelt, H;Leitinger, N
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Leitinger, N
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4.8
作者：
Fluiter, K;Sattler, W;van Berkel, TJC
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van Berkel, TJC
影响因子：
20.1
作者：
Choi SH;Harkewicz R;Lee JH;Boullier A;Almazan F;Li AC;Witztum JL;Bae YS;Miller YI
通讯作者：
Miller YI
影响因子：
7.4
作者：
Kadl A;Sharma PR;Chen W;Agrawal R;Meher AK;Rudraiah S;Grubbs N;Sharma R;Leitinger N
通讯作者：
Leitinger N