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摘要
Proprotein convertase subtilisin/Kexin type 9 (PCSK9) 是一种分泌性丝氨酸蛋白酶,在调节生理和病理过程中发挥多种生物学功能。 PCSK9 抑制剂降低循环 LDL 胆固醇水平,对动脉粥样硬化 (AS) 具有众所周知的预防和治疗作用。尽管如此,越来越多的证据表明 PCSK9 对血管壁的直接影响在动脉粥样硬化进展中也起着重要作用。与其他血管细胞相比,PCSK9的很大一部分来源于血管平滑肌细胞(VSMC)。因此,定义 VSMC 衍生的 PCSK9 对 VSMC 表型转换、细胞凋亡、自噬、炎症、泡沫细胞形成和钙化等反应变化的影响,有助于我们更好地了解 VSMC 对动脉粥样硬化过程的“多效性”作用。此外,我们对PCSK9在体内控制VSMC功能的机制的了解还远远不够。本综述旨在全面评估和分析我们对影响 VSMC 功能的 PCSK9 作用及其在动脉粥样硬化病变发展中的机制的知识现状。对 PCSK9 对 VSMC 影响的机制理解将进一步巩固针对 AS 的新治疗策略的成功。
关键词: Proprotein convertase subtilisin/kexin type 9 (PCSK9)
Current Medicinal Chemistry
Title:Effect of PCSK9 on Vascular Smooth Muscle Cell Functions: A New Player in Atherosclerosis
Volume: 28 Issue: 36
关键词: Proprotein convertase subtilisin/kexin type 9 (PCSK9)
摘要: Proprotein convertase subtilisin/Kexin type 9 (PCSK9) is a secretory serine protease that plays multiple biological functions in the regulation of physiological and pathological processes. PCSK9 inhibitors decrease the circulating LDL-cholesterol level with well-known preventive and therapeutic effects on atherosclerosis (AS). Still, increasing evidence shows that the direct impact of PCSK9 on the vascular wall also plays an important role in atherosclerotic progression. Compared with other vascular cells, a large proportion of PCSK9 is originated from vascular smooth muscle cells (VSMC). Therefore, defining the effect of VSMC-derived PCSK9 on response changes, such as phenotypic switch, apoptosis, autophagy, inflammation, foam cell formation, and calcification of VSMC, helps us better understand the “pleiotropic” effects of VSMC on the atherosclerotic process. In addition, our understanding of the mechanisms of PCSK9 controlling VSMC functions in vivo is far from enough. This review aims to holistically evaluate and analyze the current state of our knowledge regarding PCSK9 actions affecting VSMC functions and its mechanism in atherosclerotic lesion development. A mechanistic understanding of PCSK9 effects on VSMC will further underpin the success of a new therapeutic strategy targeting AS.
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Cite this article as:
Effect of PCSK9 on Vascular Smooth Muscle Cell Functions: A New Player in Atherosclerosis, Current Medicinal Chemistry 2021; 28 (36) . https://dx.doi.org/10.2174/0929867328666210531150302
DOI https://dx.doi.org/10.2174/0929867328666210531150302 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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