Age-related vascular stiffening: causes and consequences.
Age-related vascular stiffening: causes and consequences.
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DOI：
10.3389/fgene.2015.00112
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发表时间：
2015
影响因子：
3.7
通讯作者：
Reinhart-King CA
中科院分区：
文献类型：
--
作者：
Kohn JC;Lampi MC;Reinhart-King CA
动脉硬化随着年龄的增长而发生，并且与心血管疾病的进展密切相关。硬化最常在整个血管水平上进行研究，因为大动脉僵硬度的增加会对心脏造成更大的压力，导致心力衰竭。然而有趣的是，最近的证据表明，血管硬化增加的影响超出了组织范围，并且还可能对细胞功能产生有害的微观影响。改变的细胞外基质（ECM）结构已被认为是动脉粥样硬化前状态的关键组成部分。在此，讨论了与年龄相关的血管硬化的根本原因，重点是 ECM 蛋白的年龄相关交联以及基质沉积的增加。描述了在宏观和微观尺度上测量血管硬化的方法，从临床上进行的脉搏波速度测量到主要在研究实验室中进行的微观测量。此外，最近研究动脉僵硬度和与僵硬相关的 ECM 变化如何导致内皮功能障碍的研究也将得到回顾。我们将重点介绍 ECM 蛋白质组成的变化如何导致血管壁动脉粥样硬化。最后，我们将讨论最近的研究，该研究表明内皮细胞（EC）对动脉硬化具有机械敏感性，其中僵硬度的变化可以直接影响内皮细胞的健康。总体而言，最近的研究表明，硬化是一个重要的临床目标，不仅因为它对心脏有潜在的有害影响，而且因为它会促进血管壁细胞水平的功能障碍，从而导致病理性动脉粥样硬化状态。
Arterial stiffening occurs with age and is closely associated with the progression of cardiovascular disease. Stiffening is most often studied at the level of the whole vessel because increased stiffness of the large arteries can impose increased strain on the heart leading to heart failure. Interestingly, however, recent evidence suggests that the impact of increased vessel stiffening extends beyond the tissue scale and can also have deleterious microscale effects on cellular function. Altered extracellular matrix (ECM) architecture has been recognized as a key component of the pre-atherogenic state. Here, the underlying causes of age-related vessel stiffening are discussed, focusing on age-related crosslinking of the ECM proteins as well as through increased matrix deposition. Methods to measure vessel stiffening at both the macro- and microscale are described, spanning from the pulse wave velocity measurements performed clinically to microscale measurements performed largely in research laboratories. Additionally, recent work investigating how arterial stiffness and the changes in the ECM associated with stiffening contributed to endothelial dysfunction will be reviewed. We will highlight how changes in ECM protein composition contribute to atherosclerosis in the vessel wall. Lastly, we will discuss very recent work that demonstrates endothelial cells (ECs) are mechano-sensitive to arterial stiffening, where changes in stiffness can directly impact EC health. Overall, recent studies suggest that stiffening is an important clinical target not only because of potential deleterious effects on the heart but also because it promotes cellular level dysfunction in the vessel wall, contributing to a pathological atherosclerotic state.
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