PIEZO Ion Channels in Cardiovascular Functions and Diseases

Abstract

The cardiovascular system provides blood supply throughout the body and as such is perpetually applying mechanical forces to cells and tissues. Thus, this system is primed with mechanosensory structures that respond and adapt to changes in mechanical stimuli. Since their discovery in 2010, PIEZO ion channels have dominated the field of mechanobiology. These have been proposed as the long-sought-after mechanosensitive excitatory channels involved in touch and proprioception in mammals. However, more and more pieces of evidence point to the importance of PIEZO channels in cardiovascular activities and disease development. PIEZO channel-related cardiac functions include transducing hemodynamic forces in endothelial and vascular cells, red blood cell homeostasis, platelet aggregation, and arterial blood pressure regulation, among others. PIEZO channels contribute to pathological conditions including cardiac hypertrophy and pulmonary hypertension and congenital syndromes such as generalized lymphatic dysplasia and xerocytosis. In this review, we highlight recent advances in understanding the role of PIEZO channels in cardiovascular functions and diseases. Achievements in this quickly expanding field should open a new road for efficient control of PIEZO-related diseases in cardiovascular functions.

Mechanosensitive membrane domains regulate calcium entry in arterial endothelial cells to protect against inflammation

“…Since the ion channel TRPV4 is implicated in endothelial Ca 2+ “sparklet” activity in mouse arteries ( 14 ), we tested the role of TRPV4 channels by adding the TRPV4-specific antagonist GSK205 during imaging of GCaMP-HAECs under flow and found that it suppressed Ca 2+ activity ( Figure 5B and Supplemental Figure 5C ). Considering the role of PIEZO channels as sensors of blood flow ( 35 , 36 ), we also tested the role of PIEZO1 by adding the stretch-activated cation channel blocker GsMTx-4 ( 37 ), which did not affect Ca 2+ oscillations at the downstream end ( Supplemental Figure 5D ). The cumulative data indicate that TRPV4 is required for oscillatory Ca 2+ entry at polarized caveolin-1–rich domains, where active eNOS was observed in flow-exposed elongated ECs.…”