Trache Andreea, Massett Michael P, Woodman Christopher R
Department of Medical Physiology, Texas A&M University Health Science Center, Bryan, TX, United States; Department of Biomedical Engineering, Texas A&M University, College Station, TX, United States.
Department of Kinesiology and Sport Management, Texas Tech University, Lubbock, TX, United States.
Curr Top Membr. 2020;86:217-253. doi: 10.1016/bs.ctm.2020.08.008. Epub 2020 Oct 12.
Vascular smooth muscle cells (VSMC) are now considered important contributors to the pathophysiological and biophysical mechanisms underlying arterial stiffening in aging. Here, we review mechanisms whereby VSMC stiffening alters vascular function and contributes to the changes in vascular stiffening observed in aging and cardiovascular disease. Vascular stiffening in arterial aging was historically associated with changes in the extracellular matrix; however, new evidence suggests that endothelial and vascular smooth muscle cell stiffness also contribute to overall blood vessel stiffness. Furthermore, VSMC play an integral role in regulating matrix deposition and vessel wall contractility via interaction between the actomyosin contractile unit and adhesion structures that anchor the cell within the extracellular matrix. Aged-induce phenotypic modulation of VSMC from a contractile to a synthetic phenotype is associated with decreased cellular contractility and increased cell stiffness. Aged VSMC also display reduced mechanosensitivity and adaptation to mechanical signals from their microenvironment due to impaired intracellular signaling. Finally, evidence for decreased contractility in arteries from aged animals demonstrate that changes at the cellular level result in decreased functional properties at the tissue level.
血管平滑肌细胞（VSMC）现在被认为是衰老过程中动脉僵硬背后病理生理和生物物理机制的重要促成因素。在此，我们综述了VSMC僵硬改变血管功能并导致衰老和心血管疾病中观察到的血管僵硬变化的机制。动脉衰老中的血管僵硬在历史上与细胞外基质的变化有关；然而，新证据表明内皮细胞和血管平滑肌细胞的僵硬也会导致整体血管僵硬。此外，VSMC通过肌动球蛋白收缩单元与将细胞锚定在细胞外基质中的粘附结构之间的相互作用，在调节基质沉积和血管壁收缩性方面发挥着不可或缺的作用。衰老诱导的VSMC从收缩表型向合成表型的表型调节与细胞收缩性降低和细胞僵硬增加有关。由于细胞内信号受损，衰老的VSMC对来自其微环境的机械信号的机械敏感性和适应性也降低。最后，来自老年动物动脉收缩性降低的证据表明，细胞水平的变化会导致组织水平的功能特性降低。
