Gargiulo Simona, Gamba Paola, Testa Gabriella, Leonarduzzi Gabriella, Poli Giuseppe
Department of Clinical and Biological Sciences, University of Torino, San Luigi Hospital, 10043 Orbassano, Torino, Italy.
J Physiol. 2016 Apr 15;594(8):2095-113. doi: 10.1113/JP271168. Epub 2016 Jan 19.
The ageing endothelium progressively loses its remarkable and crucial ability to maintain homeostasis of the vasculature, as it acquires a proinflammatory phenotype. Cellular and structural changes gradually accumulate in the blood vessels, and markedly in artery walls. Most changes in aged arteries are comparable to those occurring during the atherogenic process, the latter being more marked: pro-oxidant and proinflammatory molecules, mainly deriving from or triggered by oxidized low density lipoproteins (oxLDLs), are undoubtedly a major driving force of this process. Oxysterols, quantitatively relevant components of oxLDLs, are likely candidate molecules in the pathogenesis of vascular ageing, because of their marked pro-oxidant, proinflammatory and proapoptotic properties. An increasing bulk of experimental data point to the contribution of a variety of oxysterols of pathophysiological interest, also in the age-related genesis of endothelium dysfunction, intimal thickening due to lipid accumulation, and smooth muscle cell migration and arterial stiffness due to increasing collagen deposition and calcification. This review provides an updated analysis of the molecular mechanisms whereby oxysterols accumulating in the wall of ageing blood vessels may 'activate' endothelial and monocytic cells, through expression of an inflammatory phenotype, and 'convince' smooth muscle cells to proliferate, migrate and, above all, to act as fibroblast-like cells.
随着内皮细胞获得促炎表型,衰老的内皮细胞逐渐丧失其维持血管系统稳态的卓越且关键的能力。细胞和结构变化在血管中逐渐累积,在动脉壁中尤为明显。老年动脉中的大多数变化与动脉粥样硬化形成过程中发生的变化相似,后者更为显著:主要源自氧化型低密度脂蛋白(oxLDLs)或由其触发的促氧化剂和促炎分子无疑是这一过程的主要驱动力。氧甾醇是oxLDLs的定量相关成分,由于其显著的促氧化、促炎和促凋亡特性,可能是血管衰老发病机制中的候选分子。越来越多的实验数据表明,各种具有病理生理学意义的氧甾醇也在与年龄相关的内皮功能障碍、脂质积累导致的内膜增厚以及平滑肌细胞迁移和由于胶原蛋白沉积和钙化增加导致的动脉僵硬的发生中起作用。本综述对衰老血管壁中积累的氧甾醇可能通过表达炎症表型“激活”内皮细胞和单核细胞,并“促使”平滑肌细胞增殖、迁移,最重要的是,使其表现为成纤维细胞样细胞的分子机制进行了更新分析。