Defective Protein Catabolism in Atherosclerotic Vascular Inflammation.
Defective Protein Catabolism in Atherosclerotic Vascular Inflammation.
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DOI：
10.3389/fcvm.2017.00079
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发表时间：
2017
影响因子：
3.6
通讯作者：
Miyazaki A
中科院分区：
文献类型：
--
作者：
Miyazaki T;Miyazaki A
动脉粥样硬化血管中的血管炎症在血脂异常患者的整个动脉树中传播，从而加速动脉粥样硬化进展。为了阐明血管炎症的机制，大多数先前的研究集中在响应于血管活性刺激而发送的炎症相关信号。然而，了解正常血管如何变得有缺陷并开始退化也很重要。越来越多的证据表明，在动脉粥样硬化血管中，主要的蛋白质催化途径，包括泛素-蛋白酶体、自噬和钙蛋白酶系统受到干扰，并导致动脉粥样硬化的发病机制。事实上，泛素-蛋白酶体途径的失调导致缺陷蛋白在血管中的积累，导致血管内皮功能障碍和受影响细胞的凋亡。受损的自噬-溶酶体降解影响平滑肌细胞转化和增殖，以及内皮完整性和细胞尸体的吞噬清除。钙蛋白酶系统的失调赋予内皮细胞、平滑肌细胞和巨噬细胞致动脉粥样硬化的特性。在这篇综述文章中，我们将讨论目前的信息，有缺陷的蛋白catalysts在动脉粥样硬化血管及其潜在的相互关系与炎症相关的信号。
Vascular inflammation in atheroprone vessels propagates throughout the arterial tree in dyslipidemic patients, thereby accelerating atherosclerotic progression. To elucidate the mechanism of vascular inflammation, most previous studies have focused on inflammation-related signals that are sent in response to vasoactive stimuli. However, it is also important to understand how normal blood vessels become defective and start degenerating. Growing evidence suggests that major protein catabolism pathways, including the ubiquitin-proteasome, autophagy, and calpain systems, are disturbed in atheroprone vessels and contribute to the pathogenesis of atherosclerosis. Indeed, dysregulation of ubiquitin–proteasome pathways results in the accumulation of defective proteins in blood vessels, leading to vascular endothelial dysfunction and apoptosis in affected cells. Impaired autophagy-lysosomal degradation affects smooth muscle cell transformation and proliferation, as well as endothelial integrity and phagocytic clearance of cellular corpses. Dysregulation of the calpain system confers proatherogenic properties to endothelial cells, smooth muscle cells, and macrophages. In this review article, we will discuss the current information available on defective protein catabolism in atheroprone vessels and its potential interrelation with inflammation-related signals.