Vascular calcium signalling and ageing.
Vascular calcium signalling and ageing.
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DOI：
10.1113/jp280950
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发表时间：
2021-12
影响因子：
5.5
通讯作者：
Jensen, Lars Jorn
中科院分区：
文献类型：
--
作者：
Harraz, Osama F.;Jensen, Lars Jorn
关键词：
细胞内Ca 2+水平的变化对血管功能和血压调节有重要影响。血管平滑肌细胞（SMC）和内皮细胞（EC）以不同的方式协调血管活动，通常涉及高度特异性的Ca 2+信号波动。衰老是心血管疾病的主要危险因素，但衰老本身对血管Ca 2+信号传导的影响尚未得到足够的重视。我们回顾了与年龄相关的Ca 2+信号与血管结构和功能的变化的文献。在几个血管床中的血管张力失调与SMC电压门控性Ca 2+通道、Ca 2+激活的K+通道或TRPC 6通道的异常表达或活性有关。其中一些影响与改变的小窝密度，microRNA表达或20-HETE丰度有关。细胞内钙库处理在衰老过程中主要通过减少细胞内钙释放通道和钙再摄取或外排泵的表达而受到抑制。线粒体Ca 2+摄取增加，导致氧化应激，也可能在SMC过度收缩和结构重塑中发挥作用。在内皮细胞中，老化对自发和诱发的Ca 2+瞬变以及EC-SMC界面的结构变化产生了不同的影响。改变的Ca 2+信号传导对肌源性张力、内皮依赖性血管舒张和血管结构的协同作用可能导致血压失调和关键器官的血流分布缺陷。随着世界老龄化人口的增加，未来的研究应针对解决特定的衰老诱导的Ca 2+信号转导缺陷，以对抗即将加速的血管老化和心血管疾病风险的增加。衰老通常与血管功能的变化有关。阻力血管-控制外周阻力，从而控制血压-表现出血管张力改变和血管传导受损。这些变化可以追溯到阻力血管、平滑肌细胞（SMC）和内皮细胞（EC）的构建模块中的Ca 2+信号传导缺陷。渗透或响应Ca 2+信号的离子通道活性的改变、Ca 2+的细胞内处理和线粒体功能障碍与衰老相关的血管功能障碍有关。
Changes in cellular Ca2+ levels have major influences on vascular function and blood pressure regulation. Vascular smooth muscle cells (SMCs) and endothelial cells (ECs) orchestrate vascular activity in distinct ways, often involving highly specific fluctuations in Ca2+ signalling. Ageing is a major risk factor for cardiovascular diseases, but the impact of ageing perse on vascular Ca2+ signalling has received insufficient attention. We reviewed the literature for age-related changes in Ca2+ signalling in relation to vascular structure and function. Vascular tone dysregulation in several vascular beds has been linked to abnormal expression or activity of SMC voltage-gated Ca2+ channels, Ca2+-activated K+ channels or TRPC6 channels. Some of these effects were linked to altered caveolae density, microRNA expression or 20-HETE abundance. Intracellular store Ca2+ handling was suppressed in ageing mainly via reduced expression of intracellular Ca2+ release channels, and Ca2+ reuptake or efflux pumps. An increase in mitochondrial Ca2+ uptake, leading to oxidative stress, could also play a role in SMC hypercontractility and structural remodelling in ageing. In ECs, ageing entailed diverse effects on spontaneous and evoked Ca2+ transients, as well as structural changes at the EC-SMC interface. The concerted effects of altered Ca2+ signalling on myogenic tone, endothelium-dependent vasodilatation, and vascular structure are likely to contribute to blood pressure dysregulation and blood flow distribution deficits in critical organs. With the increase in the world’s ageing population, future studies should be directed at solving specific ageing-induced Ca2+ signalling deficits to combat the imminent accelerated vascular ageing and increased risk of cardiovascular diseases. Ageing is often associated with a change in vascular function. Resistance vessels – which control peripheral resistance, and therefore blood pressure – demonstrate altered vascular tone and impaired vascular conduction. These changes can be traced back to defective Ca2+ signalling in the building blocks of resistance vessels, smooth muscle cells (SMCs) and endothelial cells (ECs). Alterations in the activity of ion channels that permeate or respond to Ca2+ signals, intracellular handling of Ca2+ and mitochondrial dysfunction have been implicated in ageing-associated vascular dysfunction.