Editorial: Calcium regulation and Mechano-transduction in vascular diseases: obligatory role of transient receptor potential and Piezo channels
Year: 2024
Type: editorial
Abstract: The Fron�ers Research Topic "Calcium Regula�on and Mechano-transduc�on in Vascular Diseases: Obligatory Role of Transient Receptor Poten�al and Piezo Channels" encompasses 4 ar�cles highligh�ng various aspects of the mechanical forces sensed by vascular cells that are translated into intracellular Ca 2+ signaling events that regulate vascular func�on. These aspects include Piezo1 channels and the regula�on of vascular tone by altering vasoconstric�on and vasorelaxa�on. The second focus is aligned with vascular remodeling, i.e., Peizo's role in cardiac fibrosis and vascular calcifica�on.During pregnancy, the body undergoes cardiovascular changes to meet the metabolic demands of both the mother and the fetus. As a result, there is an increase in uterine arterial blood flow. However, despite the increase in blood flow, there is no change in blood pressure. This is because the uterine arteries (UA) dilate to accommodate the greater blood flow. The Piezo1 channel, which is highly expressed in endothelial cells (EC) and smooth muscle cells (SMCs) of resistance arteries such as UAs, is responsible for sensing mechanical forces. In this research topic, Arishe et al. sought to examine the underlying mechanisms of Piezo1 signaling in the UAs of pseudo-pregnant rats 9 . They found that concentra�on-dependent relaxa�on to the Piezo1 agonist Yoda1 was greater in UAs from pseudopregnant rats when compared to virgin rats. Furthermore, they discovered that the nitric oxide synthase inhibitor L-NAME was able to atenuate Yoda1-induced relaxa�on response in UA. Thus, Arishe et al were able to demonstrate that Piezo1 channels regulate vasodila�on in the UAs of pseudo-pregnant rats in part via a NO-dependent mechanism.Pulmonary arterial hypertension (PAH) is a life-threatening condi�on characterized by increased pulmonary arterial pressure (PAP) which is caused by elevated pulmonary vascular resistance (PVR) 10 . Sustained pulmonary vasoconstric�on, concentric vascular remodeling, and other factors are major causes of direct increases in PVR and PAP in pa�ents with PAH. Current therapeu�c targets for pulmonary arterial hypertension (PAH) focus on membrane receptors and ion channels that promote vasodila�on while inhibi�ng vasoconstric�on and prolifera�on. Calcium channel blockers are frequently used to relieve pulmonary vasoconstric�on. However, the treatment proves effec�ve for only a small number of pa�ents, and many of them eventually develop resistance to it. The TRP family of ion channels plays a crucial role in store-operated calcium entry in the pulmonary circula�on and has been studied extensively as a poten�al target for therapeu�c interven�on. However, targe�ng TRP channels therapeu�cally is a challenging task due to their pharmacological non-specificity and the poten�al implica�ons for unintended effects on other �ssues. Yang et al. propose Piezo1 as a therapeu�c target for trea�ng pulmonary hypertension. 11 There is evidence of increased Piezo1 expression in the PASMCs and PAECs of pa�ents with PAH, sugges�ng Piezo1's pathological implica�on in PAH. The authors have brought up the discussion of several newly discovered Piezo1 targe�ng compounds. These compounds could prove to be promising in the clinical se�ng. The compound SalB, extracted from Chinese sage root, was shown to inhibit Piezo1 ion channels ac�vated by Yoda1 or mechanical stress 12 . The triterpenoid saponin Tubeimoside I (TBMS I) has also been demonstrated to antagonize Yoda1-induced Piezo1 channel ac�va�on 13 . These compounds are expected to become valuable pharmacological tools for examining the func�on of the Piezo1 channel. We hope that they can be u�lized to further inves�gate the pathophysiology of cardiovascular diseases, so that we can have a beter understanding of the impact of Piezo1 in vascular biology.Mechanotransduc�on is an important process in the repair and regenera�on of �ssues. However, prolonged or excessive mechanical stress is a major cause of fibrosis. Several studies have shown that various ion channels contribute to the prolifera�on, contrac�on, and secre�on of myofibroblasts. The review by Xing et al summarizes the research progress made on the role of TRP channels, Piezo1, Ca2+ release-ac�vated channels (CRAC), and others in myocardial fibrosis 14 . Some key findings covered in the review include the role of TRP channels in fibroblast differen�a�on by regula�ng intracellular Ca2+ levels. There is also evidence CRAC channels may also contribute to cardiac remodeling under pathological condi�ons. Addi�onally, Piezo1-mediated mechanotransduc�on was shown to promote cardiac hypertrophy by impairing calcium homeostasis to ac�vate calpain/calcineurin signaling 15 .Vascular calcifica�on is linked to various cardiovascular diseases. However, it is yet to be determined how Piezo1 contributes to this process. In a study by Szabo et al, they inves�gated the role of Piezo1 in human aor�c smooth muscle cells 16 . They found that HAoSMCs condi�oned with culture media that promotes calcifica�on showed higher calcium transients compared to the control group. Ac�va�on of Piezo1 channels with Yoda1 was observed to increase the rate of calcifica�on in HAoSMCs, while the Piezo1 inhibitor Dooku1 was found to inhibit the calcifica�on process. The data from the study strongly indicates that Piezo1 plays a crucial role in arterial calcifica�on.The four ar�cles presented in this special topic shed light on the significance of mechanotransduc�on in both normal and abnormal physiological condi�ons. The findings provide poten�al new avenues for trea�ng cardiovascular disease through the development of diagnos�c methods, therapeu�c drugs and clinical management strategies. However, further research is necessary to bridge the gaps in our understanding of the pathogenesis of CVD and promote progress in this field.
Source: Frontiers in Physiology
Institutions: University of Virginia, University of Padua
Language: English
Topic: Ion Channels and Receptors
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,295
OpenAlex ID: W4392236308