Canonical Transient Receptor Potential Channels and Vascular Smooth Muscle Cell Plasticity
Canonical Transient Receptor Potential Channels and Vascular Smooth Muscle Cell Plasticity
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DOI：
10.12997/jla.2020.9.1.124
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发表时间：
2020-01
影响因子：
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通讯作者：
M. Nishida;Tomohiro Tanaka;S. Mangmool;K. Nishiyama;Akiyuki Nishimura
中科院分区：
文献类型：
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作者：
M. Nishida;Tomohiro Tanaka;S. Mangmool;K. Nishiyama;Akiyuki Nishimura
血管平滑肌细胞（VSMC）在血管稳态的稳定性和紧张性调节中发挥着关键作用。 VSMC 可以在高度增殖（合成）和完全分化（收缩）表型之间来回切换，以响应血管环境的变化。 VSMC 的异常表型转换是血管疾病的一个显着特征，包括动脉粥样硬化、肺动脉高压、中风和外周动脉疾病；然而，VSMC表型转换的控制如何在病理条件下失调仍不清楚。规范瞬时受体电位（TRPC）通道作为 VSMC 病理表型转换的关键调节因子而引起人们的关注。几种 TRPC 亚家族成员蛋白（尤其是 TRPC1 和 TRPC6）在病理性 VSMC 中表达上调，据报道，药物抑制 TRPC 通道活性可改善啮齿类动物的高血压血管重塑。本综述总结了目前对 TRPC 通道在心血管可塑性中作用的理解，包括我们最近发现 TRPC6 参与缺血条件下异常的 VSMC 表型转换，并讨论了 TRPC 通道的治疗潜力。
Vascular smooth muscle cells (VSMCs) play a pivotal role in the stability and tonic regulation of vascular homeostasis. VSMCs can switch back and forth between highly proliferative (synthetic) and fully differentiated (contractile) phenotypes in response to changes in the vessel environment. Abnormal phenotypic switching of VSMCs is a distinctive characteristic of vascular disorders, including atherosclerosis, pulmonary hypertension, stroke, and peripheral artery disease; however, how the control of VSMC phenotypic switching is dysregulated under pathological conditions remains obscure. Canonical transient receptor potential (TRPC) channels have attracted attention as a key regulator of pathological phenotype switching in VSMCs. Several TRPC subfamily member proteins—especially TRPC1 and TRPC6—are upregulated in pathological VSMCs, and pharmacological inhibition of TRPC channel activity has been reported to improve hypertensive vascular remodeling in rodents. This review summarizes the current understanding of the role of TRPC channels in cardiovascular plasticity, including our recent finding that TRPC6 participates in aberrant VSMC phenotype switching under ischemic conditions, and discusses the therapeutic potential of TRPC channels.