Mechanosensitivity in Pulmonary Circulation: Pathophysiological Relevance of Stretch-Activated Channels in Pulmonary Hypertension.
Solène BarbeauGuillaume GilbertGuillaume CardouatIsabelle BaudrimontVéronique Freund-MichelChristelle GuibertRoger MarthanPierre VacherJean-François QuignardThomas DucretPublished in: Biomolecules (2021)
A variety of cell types in pulmonary arteries (endothelial cells, fibroblasts, and smooth muscle cells) are continuously exposed to mechanical stimulations such as shear stress and pulsatile blood pressure, which are altered under conditions of pulmonary hypertension (PH). Most functions of such vascular cells (e.g., contraction, migration, proliferation, production of extracellular matrix proteins, etc.) depend on a key event, i.e., the increase in intracellular calcium concentration ([Ca2+]i) which results from an influx of extracellular Ca2+ and/or a release of intracellular stored Ca2+. Calcium entry from the extracellular space is a major step in the elevation of [Ca2+]i, involving a variety of plasmalemmal Ca2+ channels including the superfamily of stretch-activated channels (SAC). A common characteristic of SAC is that their gating depends on membrane stretch. In general, SAC are non-selective Ca2+-permeable cation channels, including proteins of the TRP (Transient Receptor Potential) and Piezo channel superfamily. As membrane mechano-transducers, SAC convert physical forces into biological signals and hence into a cell response. Consequently, SAC play a major role in pulmonary arterial calcium homeostasis and, thus, appear as potential novel drug targets for a better management of PH.
Keyphrases
- pulmonary hypertension
- extracellular matrix
- pulmonary artery
- blood pressure
- protein kinase
- endothelial cells
- pulmonary arterial hypertension
- single cell
- induced apoptosis
- stem cells
- signaling pathway
- physical activity
- adipose tissue
- heart rate
- emergency department
- oxidative stress
- insulin resistance
- subarachnoid hemorrhage
- skeletal muscle
- pi k akt