Examining The Therapeutic Potential Of TRPV4 Modulation In Angiogenesis: Implications For Myocardial Infarction Recovery And Tumour Regression

Angiogenesis is the physiological process of creating new blood vessels. It is the body’s natural healing response to restore blood flow to damaged tissue. In the case of ischemic heart disease, the angiogenic response becomes crucial to increase blood supply to the heart and avoid a myocardial infarction. On the other hand, in the case of cancer progression, inhibition of the angiogenic response can be studied as a mechanism to disrupt the oxygen and nutrient supply to cancer cells, thus limiting tumour growth. Calcium ions play a crucial role in several cellular processes, including cell proliferation and cell migration. Transient Receptor Potential cation channel subfamily Vanilloid member 4 (TRPV4) is moderately permeable to Ca2+ and can be found in endothelial cells, which comprise the inner lining of blood vessels. PURPOSE: This study investigated the potential link between the TRPV4 channel and angiogenesis using an Aortic Ring Assay (ARA) mouse model. METHODS: 3-day-old C57Bl/6 pups were euthanized prior to the removal of thoracic aortas. The vessels were cleaned, cut into 1 mm wide rings, and randomized into a control group, 2 agonist groups (3 nm, 10 nm) and 2 antagonist groups (3 nm, 10 nm). By exposing the rings to a specific TRPV4 agonist (GSK1016790) and antagonist (HC067047) in comparison to the control standard growth media, we measured the length and number of new sprouts. RESULTS: The results revealed a significant (p < 0.05) decrease in the number and length of sprouts when rings were exposed to the antagonistic compound and a significant increase in sprout length when exposed to the agonist compound. CONCLUSION: This study can provide pertinent information on TRPV4's role as a mediator for intracellular signalling where inhibition and stimulation of the ion channel can potentially be a therapeutic target for vascular remodelling. Thus, leading to future research on treating and preventing diseases dealing with reduced blood flow to the heart and abnormal angiogenic growth. Moving forward, additional research in vivo will look at the synergistic potential between high-intensity aerobic exercise and the TRPV4 cation channel on angiogenesis.