Endothelial cells, endoplasmic reticulum stress and oxysterols.
Endothelial cells, endoplasmic reticulum stress and oxysterols.
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内皮细胞、内质网应激和氧固醇类。
DOI：
10.1016/j.redox.2017.07.014
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发表时间：
2017-10
期刊：
影响因子：
11.4
通讯作者：
Iuliano L
中科院分区：
文献类型：
--
作者：
Luchetti F;Crinelli R;Cesarini E;Canonico B;Guidi L;Zerbinati C;Di Sario G;Zamai L;Magnani M;Papa S;Iuliano L
氧化甾醇是一种生物活性脂类，可调节脂类新陈代谢、炎症和细胞活力，并与包括动脉粥样硬化在内的多种疾病有关。越来越多的证据将动脉粥样硬化与内皮功能障碍联系起来；事实上，内皮调节血管系统，在止血、细胞胆固醇、激素转运、信号转导和炎症等过程中发挥作用。几篇论文阐明了氧化甾醇诱导包括内皮细胞在内的不同细胞系的凋亡的能力。内皮细胞的凋亡和内皮剥脱可能是斑块侵蚀和血管血栓形成过程中的关键步骤，因此预防内皮损伤作为治疗动脉粥样硬化的一种新手段引起了人们的广泛关注。内质网(ER)是蛋白质合成和折叠的场所，是大多数细胞活动所必需的；内质网稳态的扰动导致内质网应激。这种情况会引起未折叠蛋白反应(UPR)，这是一种旨在恢复内质网稳态的适应性途径。越来越多的证据表明，UPR的慢性激活导致细胞功能障碍和死亡，最近被认为与内皮功能障碍的发病机制有关。自噬是一种基本的分解代谢机制，它将错误折叠的蛋白质和受损的细胞器运送到溶酶体进行降解，维持基础水平的自噬活性对细胞生存至关重要。一些证据表明，持续的内质网应激往往导致自噬活动的刺激，可能作为一种补偿机制来缓解内质网应激，从而导致细胞死亡。在这篇综述中，我们总结了氧化甾醇对内皮细胞影响的证据，尤其是氧化甾醇介导的内质网应激的诱导。血管内皮细胞功能障碍在动脉粥样硬化血栓形成过程中起关键作用。内质网应激是内皮细胞功能障碍的重要组成部分。氧化甾醇是动脉粥样硬化病变中发现的胆固醇的氧化产物。氧固醇是内质网应激的潜在调节剂。
Oxysterols are bioactive lipids that act as regulators of lipid metabolism, inflammation, cell viability and are involved in several diseases, including atherosclerosis. Mounting evidence linked the atherosclerosis to endothelium dysfunction; in fact, the endothelium regulates the vascular system with roles in processes such as hemostasis, cell cholesterol, hormone trafficking, signal transduction and inflammation. Several papers shed light the ability of oxysterols to induce apoptosis in different cell lines including endothelial cells. Apoptotic endothelial cell and endothelial denudation may constitute a critical step in the transition to plaque erosion and vessel thrombosis, so preventing the endothelial damaged has garnered considerable attention as a novel means of treating atherosclerosis. Endoplasmic reticulum (ER) is the site where the proteins are synthetized and folded and is necessary for most cellular activity; perturbations of ER homeostasis leads to a condition known as endoplasmic reticulum stress. This condition evokes the unfolded protein response (UPR) an adaptive pathway that aims to restore ER homeostasis. Mounting evidence suggests that chronic activation of UPR leads to cell dysfunction and death and recently has been implicated in pathogenesis of endothelial dysfunction. Autophagy is an essential catabolic mechanism that delivers misfolded proteins and damaged organelles to the lysosome for degradation, maintaining basal levels of autophagic activity it is critical for cell survival. Several evidence suggests that persistent ER stress often results in stimulation of autophagic activities, likely as a compensatory mechanism to relieve ER stress and consequently cell death. In this review, we summarize evidence for the effect of oxysterols on endothelial cells, especially focusing on oxysterols-mediated induction of endoplasmic reticulum stress. Endothelial cells dysfunction is critical in the process of atherothrombosis. Endoplasmic reticulum stress is a key component in endothelial cell dysfunction. Oxysterols are oxidation products of cholesterol found in atherosclerosis lesions. Oxysterols are potential modulators of endoplasmic reticulum stress.
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影响因子：
16
作者：
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通讯作者：
Ron, D
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7.3
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