脂毒性、内质网应激和心血管疾病:目前的理解和未来的方向。

Smriti Shreya, Md Jahangir Alam, Anupriya, Saumya Jaiswal, Vibha Rani, Buddhi Prakash Jain
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引用次数: 0

摘要

内质网(ER)是一种亚细胞器,负责蛋白质的正确折叠、脂质生物合成、钙储存和各种翻译后修饰。在ER功能紊乱的过程中,未折叠或错误折叠的蛋白质积聚在ER腔内,并启动下游信号传导,称为未折叠蛋白质反应(UPR)。UPR信号通路参与脂解、三酰甘油合成、脂肪生成、甲羟戊酸途径和低密度脂蛋白受体循环。内质网应激还通过改变参与脂质合成或修饰的酶的水平来影响脂质代谢,并导致脂毒性。脂质代谢与心脏病密切相关,因为脂质代谢的失调会导致各种心血管疾病的发展。几项研究表明,脂毒性是心血管疾病的重要因素之一。在这篇综述中,我们将讨论内质网应激如何影响脂质代谢及其在心血管疾病发展中的相互作用。此外,将总结目前可用于靶向各种心血管疾病的ER应激和脂质代谢的治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Lipotoxicity, ER Stress, and Cardiovascular Disease: Current Understanding and Future Directions.

The endoplasmic reticulum (ER) is a sub-cellular organelle that is responsible for the correct folding of proteins, lipid biosynthesis, calcium storage, and various post-translational modifications. In the disturbance of ER functioning, unfolded or misfolded proteins accumulate inside the ER lumen and initiate downstream signaling called unfolded protein response (UPR). The UPR signaling pathway is involved in lipolysis, triacylglycerol synthesis, lipogenesis, the mevalonate pathway, and low-density lipoprotein receptor recycling. ER stress also affects lipid metabolism by changing the levels of enzymes that are involved in the synthesis or modifications of lipids and causing lipotoxicity. Lipid metabolism and cardiac diseases are in close association as the deregulation of lipid metabolism leads to the development of various cardiovascular diseases (CVDs). Several studies have suggested that lipotoxicity is one of the important factors for cardiovascular disorders. In this review, we will discuss how ER stress affects lipid metabolism and their interplay in the development of cardiovascular disorders. Further, the current therapeutics available to target ER stress and lipid metabolism in various CVDs will be summarized.

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