当前位置: X-MOL 学术Cardiol. Rev. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Cholesterol Paradigm and Beyond in Atherosclerotic Cardiovascular Disease: Cholesterol, Sterol Regulatory Element-Binding Protein, Inflammation, and Vascular Cell Mobilization in Vasculopathy
Cardiology in Review ( IF 2.1 ) Pub Date : 2022-09-01 , DOI: 10.1097/crd.0000000000000406
Ruihai Zhou 1 , George A Stouffer 1 , William H Frishman 2
Affiliation  

Hypercholesterolemia is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD). How cholesterol and its carrier lipoproteins are involved in ASCVD is still under extensive investigation. Satins are thus far the best-proven class of cholesterol-lowering medications to improve the clinical outcomes of ASCVD. Statins specifically inhibit the rate-limiting enzyme 3-hydroxy-3-methylglutaryl-CoA reductase of the mevalonate pathway for cholesterol biosynthesis. The widely accepted theory is that statins inhibit the hepatic cholesterol synthesis causing upregulation of hepatocyte low-density lipoprotein (LDL) receptor; receptor-mediated LDL uptake and metabolism in the liver results in reduction of circulating LDL cholesterol, which subsequently reduces vascular deposition and retention of cholesterol or LDL in atherogenesis. Nevertheless, cholesterol biosynthesis is ubiquitous, also in extrahepatic cells including those in vascular wall, under tight regulation by sterol regulatory element-binding protein (SREBP), the master gene transcription factor governing cholesterol biosynthesis. Studies have shown that SREBP can be upregulated in vascular wall subject to injury or stent implantation. SREBP can be activated by proinflammatory and mitogenic factors in vascular cells, leading to hyperactive mevalonate pathway, which promotes vascular cell mobilization, further proinflammatory and mitogenic factor release from vascular cells, and vascular inflammation. In this article, we review the cellular cholesterol homeostasis regulation by SREBP and SREBP-mediated vascular hyperactive cholesterol biosynthesis, we term vascular hypercholesterolism, in the pathogenesis of ASCVD and vasculopathy. SREBP functions as a platform bridging cholesterol, inflammation, and vascular cell mobilization in ASCVD pathogenesis. Targeting vascular hypercholesterolism could open a new avenue in fighting against ASCVD.



中文翻译:

动脉粥样硬化性心血管疾病中的胆固醇范式及其他:血管病中的胆固醇、甾醇调节元件结合蛋白、炎症和血管细胞动员

高胆固醇血症是动脉粥样硬化性心血管疾病(ASCVD)的公认危险因素。胆固醇及其载体脂蛋白如何参与 ASCVD 仍在广泛研究中。Satins 是迄今为止经过最充分验证的一类降胆固醇药物,可改善 ASCVD 的临床结果。他汀类药物特异性抑制胆固醇生物合成甲羟戊酸途径的限速酶 3-羟基-3-甲基戊二酰辅酶 A 还原酶。广泛接受的理论是他汀类药物抑制肝脏胆固醇合成,导致肝细胞低密度脂蛋白(LDL)受体上调;肝脏中受体介导的 LDL 摄取和代谢导致循环 LDL 胆固醇减少,从而减少动脉粥样硬化形成中胆固醇或 LDL 的血管沉积和滞留。然而,胆固醇生物合成是普遍存在的,在包括血管壁在内的肝外细胞中,胆固醇生物合成也受到甾醇调节元件结合蛋白(SREBP)的严格调节,甾醇调节元件结合蛋白是控制胆固醇生物合成的主基因转录因子。研究表明,在受到损伤或支架植入的血管壁中,SREBP 会上调。SREBP可被血管细胞中的促炎和促有丝分裂因子激活,导致甲羟戊酸途径过度活跃,从而促进血管细胞动员,进一步从血管细胞释放促炎和促有丝分裂因子,以及血管炎症。在本文中,我们回顾了 ASCVD 和血管病变发病机制中 SREBP 和 SREBP 介导的血管胆固醇生物合成过度活跃(我们称之为血管胆固醇过高)对细胞胆固醇稳态的调节。SREBP 在 ASCVD 发病机制中充当桥接胆固醇、炎症和血管细胞动员的平台。针对血管性高胆固醇血症可能为对抗 ASCVD 开辟一条新途径。

更新日期:2022-08-11
down
wechat
bug