Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics.
Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics.
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健康和疾病中胆固醇稳态的调节：从机制到靶向治疗。
DOI：
10.1038/s41392-022-01125-5
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发表时间：
2022-08-02
影响因子：
39.3
通讯作者：
Han, Jihong
中科院分区：
文献类型：
--
作者：
Duan, Yajun;Gong, Ke;Xu, Suowen;Zhang, Feng;Meng, Xianshe;Han, Jihong
胆固醇稳态紊乱在多种疾病的发展中起关键作用，例如心血管疾病（CVD）、神经退行性疾病和癌症，特别是其中脂质（主要是胆固醇酯）在内皮层下的巨噬细胞/泡沫细胞内的积累最终驱动动脉粥样硬化病变的形成的CVD。越来越多的研究表明，降低胆固醇水平，特别是低密度脂蛋白胆固醇水平，可以有效地保护心血管系统，预防心血管事件的发生。维持胆固醇稳态是由胆固醇生物合成、摄取、流出、运输、储存、利用和/或排泄决定的。所有这些过程都需要通过多个调控途径进行精确控制。基于胆固醇稳态的调节，已经开发了许多干预措施来通过抑制胆固醇生物合成和摄取或增强胆固醇利用和排泄来降低胆固醇。本文综述了胆固醇代谢的历史回顾和研究进展，对调节胆固醇稳态的关键分子途径的认识，临床或临床前研究中的降胆固醇干预措施，以及新的降胆固醇靶点及其临床进展。更重要的是，我们回顾和讨论这些干预措施对治疗多种疾病的益处，包括动脉粥样硬化性心血管疾病、肥胖症、糖尿病、非酒精性脂肪肝、癌症、神经退行性疾病、骨质疏松症和病毒感染。
Disturbed cholesterol homeostasis plays critical roles in the development of multiple diseases, such as cardiovascular diseases (CVD), neurodegenerative diseases and cancers, particularly the CVD in which the accumulation of lipids (mainly the cholesteryl esters) within macrophage/foam cells underneath the endothelial layer drives the formation of atherosclerotic lesions eventually. More and more studies have shown that lowering cholesterol level, especially low-density lipoprotein cholesterol level, protects cardiovascular system and prevents cardiovascular events effectively. Maintaining cholesterol homeostasis is determined by cholesterol biosynthesis, uptake, efflux, transport, storage, utilization, and/or excretion. All the processes should be precisely controlled by the multiple regulatory pathways. Based on the regulation of cholesterol homeostasis, many interventions have been developed to lower cholesterol by inhibiting cholesterol biosynthesis and uptake or enhancing cholesterol utilization and excretion. Herein, we summarize the historical review and research events, the current understandings of the molecular pathways playing key roles in regulating cholesterol homeostasis, and the cholesterol-lowering interventions in clinics or in preclinical studies as well as new cholesterol-lowering targets and their clinical advances. More importantly, we review and discuss the benefits of those interventions for the treatment of multiple diseases including atherosclerotic cardiovascular diseases, obesity, diabetes, nonalcoholic fatty liver disease, cancer, neurodegenerative diseases, osteoporosis and virus infection.
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影响因子：
29
作者：
Temel RE;Sawyer JK;Yu L;Lord C;Degirolamo C;McDaniel A;Marshall S;Wang N;Shah R;Rudel LL;Brown JM
通讯作者：
Brown JM
影响因子：
39.3
作者：
Alexander, Veronica J.;Xia, Shuting;Tsimikas, Sotirios
通讯作者：
Tsimikas, Sotirios
影响因子：
2.8
作者：
Abela, George S.;Vedre, Ameeth;Tamhane, Umesh
通讯作者：
Tamhane, Umesh
影响因子：
3.7
作者：
Shu H;Chi J;Li J;Zhang W;Lv W;Wang J;Deng Y;Hou X;Wang Y
通讯作者：
Wang Y
影响因子：
56.9
作者：
Altmann, SW;Davis, HR;Graziano, MP
通讯作者：
Graziano, MP