Solano Alfredo Sanchez, Lavanderos Boris, Metwally Elsayed, Earley Scott
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, New York, USA.
Department of Cytology and Histology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt.
Am J Hypertens. 2025 Feb 18;38(3):151-160. doi: 10.1093/ajh/hpae134.
Transmural pressure and shear stress are mechanical forces that profoundly affect the smooth muscle cells (SMCs) comprising the vascular wall and the endothelial cells (ECs) lining the lumen. Pressure and flow are detected by mechanosensors in these cells and translated into appropriate responses to regulate blood pressure and flow. This review focuses on the role of the transient receptor potential (TRP) superfamily of cation channels in this process. We discuss how specific members of the TRP superfamily (TRPC6, TRPM4, TRPV1, TRPV4, and TRPP1) regulate the resting membrane and intracellular Ca2+ levels in SMCs and ECs to promote changes in vascular tone in response to intraluminal pressure and shear stress. Although TRP channels participate in vascular mechanotransduction, little evidence supports their intrinsic mechanosensitivity. Therefore, we also examine the evidence exploring the force-sensitive signal transduction pathways acting upstream of vascular TRP channels. Understanding the interplay between mechanosensors, force-induced signaling cascades, and TRP channels holds promise for the development of targeted therapies for diseases caused by vascular dysfunction.
跨壁压力和剪切应力是机械力，它们深刻影响构成血管壁的平滑肌细胞（SMC）和衬里管腔的内皮细胞（EC）。这些细胞中的机械传感器检测压力和流量，并将其转化为适当的反应以调节血压和流量。本综述重点关注阳离子通道瞬时受体电位（TRP）超家族在此过程中的作用。我们讨论TRP超家族的特定成员（TRPC6、TRPM4、TRPV1、TRPV4和TRPP1）如何调节SMC和EC中的静息膜电位和细胞内Ca2+水平，以响应管腔内压力和剪切应力促进血管张力的变化。尽管TRP通道参与血管机械转导，但几乎没有证据支持它们的内在机械敏感性。因此，我们还研究了探索作用于血管TRP通道上游的力敏信号转导途径的证据。了解机械传感器、力诱导的信号级联反应和TRP通道之间的相互作用，有望为开发针对血管功能障碍引起的疾病的靶向治疗方法带来希望。
