Smooth Muscle Phenotypic Diversity: Effect on Vascular Function and Drug Responses.
Smooth Muscle Phenotypic Diversity: Effect on Vascular Function and Drug Responses.
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DOI：
10.1016/bs.apha.2016.07.003
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发表时间：
2017-01-01
期刊：
影响因子：
--
通讯作者：
Fisher, S A
中科院分区：
文献类型：
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作者：
Fisher, S A
最简单的血流阻力是由血管平滑肌(VSM)收缩状态的变化调节的，这是肌球蛋白激酶和磷酸酶竞争活性的函数，决定了肌球蛋白ATPase马达蛋白的磷酸化和活性。相比之下，人类和其他哺乳动物的血管系统极其复杂，而且受到高度监管。这种复杂性在很大程度上来自于平滑肌内的表型多样性，反映在调节血管张力的信号通路的功率输出和反应上截然不同，据推测，数千年来一直在进化以优化血管功能及其控制。VSM张力的高度调节性质，被描述为药物-机械耦合，可能是临床上使用的许多类别的药物的基础，这些药物通过激活或抑制这些信号通路来改变血管张力。本文将首先描述VSM的表型多样性，然后介绍信号、肌丝和钙循环蛋白的分子多样性如何影响动脉平滑肌功能和药物反应的具体例子。
At its simplest resistance to blood flow is regulated by changes in the state of contraction of the vascular smooth muscle (VSM), a function of the competing activities of the myosin kinase and phosphatase determining the phosphorylation and activity of the myosin ATPase motor protein. In contrast, the vascular system of humans and other mammals is incredibly complex and highly regulated. Much of this complexity derives from phenotypic diversity within the smooth muscle, reflected in very differing power outputs and responses to signaling pathways that regulate vessel tone, presumably having evolved over the millennia to optimize vascular function and its control. The highly regulated nature of VSM tone, described as pharmacomechanical coupling, likely underlies the many classes of drugs in clinical use to alter vascular tone through activation or inhibition of these signaling pathways. This review will first describe the phenotypic diversity within VSM, followed by presentation of specific examples of how molecular diversity in signaling, myofilament, and calcium cycling proteins impacts arterial smooth muscle function and drug responses.