摘要
虽然在过去几十年,对动脉粥样硬化和动脉粥样硬化进展的病理生理的认知一直是心血管疾病研究的主要目标,但是底层斑块不稳定性的确切机制仍不清楚。斑块的破裂和内腔血栓的形成大部分由坏死核心(NC)的扩散决定。而坏死中心的扩散是由各种机制驱动的,包括加速巨噬细胞凋亡和有缺陷的吞噬清除(缺陷胞葬作用)氧化应激与NC的扩散有关:实际上,许多被氧化的化合物和进程有助于巨噬细胞的凋亡;此外,聚合不饱和脂肪酸的氧化衍生物也促进缺血胞葬作用,最终导致NC扩散。在过去几年间,进行了对内质网(ER)应激的作用的研究,以期更好的定义它对NC扩散影响的可能贡献。凋亡细胞在易损斑块的异常量已经被证明既与持续ER应激又与对生存和保护性基因的表达相关,例如未折叠蛋白反应或/和细胞核erytroid相关因子2。这篇综述作者着重介绍氧化和内质网应激在触发和统筹动脉粥样硬化斑块的脆弱性的可喜的成果。
关键词: 细胞凋亡,动脉粥样硬化,胞葬作用,内质网应激,坏死中心,氧化应激,易损斑块
Current Medicinal Chemistry
Title:The Atherosclerotic Plaque Vulnerability: Focus on the Oxidative and Endoplasmic Reticulum Stress in Orchestrating the Macrophage Apoptosis in the Formation of the Necrotic Core
Volume: 22 Issue: 13
Author(s): Luciano Cominacini, Ulisse Garbin, Chiara Mozzini, Chiara Stranieri, Andrea Pasini and Erika Solani, Irene Alessandra Tinelli and Anna Fratta Pasini
Affiliation:
关键词: 细胞凋亡,动脉粥样硬化,胞葬作用,内质网应激,坏死中心,氧化应激,易损斑块
摘要: Although the understanding the pathophysiology of atherogenesis and atherosclerosis progression has been one of the major goals of cardiovascular research during the last decades, the precise mechanisms underlying plaque destabilization are still unknown. The disruption of the plaque and the thrombosis in the lumen that are mostly determined by the expansion of the necrotic core (NC) are driven by various mechanisms, including accelerated macrophage apoptosis and defective phagocytic clearance (defective efferocytosis). Oxidative stress is implicated in the expansion of the NC: in fact, many oxidized compounds and processes contribute to the macrophage apoptosis; in addition, the oxidized derivatives of polyunsatured fatty acids promote defective efferocytosis, with the final result of NC expansion. In the last years the role of the endoplasmic reticulum (ER) stress is under investigation to better define its possible contribution in affecting the NC expansion. The abnormal amount of apoptotic cells in the vulnerable plaque has been demonstrated to be related both to the sustained ER stress and to the expression of survival and protective genes, such as the unfolded protein response or/and the nuclear erytroid- related factor 2. In this review the authors focus on the promising results of the oxidative and ER stress in contributing to triggering and orchestrating the atherosclerotic plaque vulnerability.
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Luciano Cominacini, Ulisse Garbin, Chiara Mozzini, Chiara Stranieri, Andrea Pasini and Erika Solani, Irene Alessandra Tinelli and Anna Fratta Pasini , The Atherosclerotic Plaque Vulnerability: Focus on the Oxidative and Endoplasmic Reticulum Stress in Orchestrating the Macrophage Apoptosis in the Formation of the Necrotic Core, Current Medicinal Chemistry 2015; 22 (13) . https://dx.doi.org/10.2174/0929867322666150311150829
DOI https://dx.doi.org/10.2174/0929867322666150311150829 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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