What is it about?

Endothelial cells from lung (pulmonary) arteries are important for pulmonary blood pressure regulation. Calcium ions are critical for the normal function of endothelial cells. We found that TRPV4, a protein that allows calcium ions to enter into endothelial cells, maintains low pulmonary blood pressure. Pulmonary hypertension is a serious disorder characterized by high pulmonary blood pressure. Our data show that a loss of endothelial TRPV4 activity raises pulmonary blood pressure in pulmonary hypertension.

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Why is it important?

Endothelial cell TRPV4 is known to have harmful effects in lung injury and edema. Although we knew that TRPV4 is active under healthy conditions, its role in maintaining normal function was unknown. We provide the first evidence that endothelial TRPV4 is essential for maintaining normal pulmonary blood pressure. Data on pulmonary arteries from patients provide clinically relevant information about the impairment of endothelial TRPV4 in pulmonary hypertension. Our results also reveal specific proteins that target endothelial TRPV4 and impair its activity in pulmonary hypertension. This information may help identify new treatment strategies for pulmonary hypertension.


1) Our manuscript provides the first evidence for the physiological role of pulmonary endothelial TRPV4. Our data also show that impaired endothelial TRPV4 from pulmonary arteries is a new mechanism for elevated pulmonary blood pressure. 2) Our data, in combination with previously published results, suggest that endothelial TRPV4 has different functional roles in lung capillaries and arteries. Moreover, endothelial TRPV4 may be differently affected in capillaries and arteries under disease conditions. 3) TRPV4 is expressed in many cell types in the body. Therefore, TRPV4 agonist therapy is likely to be associated with undesired effects. Instead, targeting the proteins that affect TRPV4 activity in disease conditions may be a better therapeutic strategy.

Swapnil Sonkusare
University of Virginia

Read the Original

This page is a summary of: Caveolar peroxynitrite formation impairs endothelial TRPV4 channels and elevates pulmonary arterial pressure in pulmonary hypertension, Proceedings of the National Academy of Sciences, April 2021, Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.2023130118.
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