EXPLORING TRPV4 MODULATION IN ANGIOGENESIS: IMPLICATIONS FOR ENHANCING AEROBIC CAPACITY AND MUSCLE PERFUSION

Author(s): MALKA, G., BERGDAHL, A., Institution: CONCORDIA UNIVERSITY , Country: CANADA, Abstract-ID: 644

INTRODUCTION:
Angiogenesis is a physiological process resulting in the formation of new capillaries from existing vascular networks. Through exercise, this process occurs as an adaptive response to improve blood-tissue exchange properties by increasing surface area for oxygen diffusion, nutrient uptake, and elimination of waste products. Thus, angiogenesis is often associated with improvements in cardiovascular hemodynamics and metabolic activity through changes in capillary density. Calcium ions (Ca2+) play a crucial role as signal transducers 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 highly expressed in endothelial cells, which comprise the inner lining of blood vessels. The activation of TRPV4, thus inducing angiogenesis through a channel-specific agonist (GSK1016790), remains relatively unexplored in current research. This study aimed to solidify the link between TRPV4 and angiogenesis using an Aortic Ring Assay (ARA) thereby providing implications for enhancing aerobic capacity and muscle perfusion during exercise.
METHODS:
Three-day-old C57Bl/6 pups were euthanized, and their thoracic aortas were surgically removed. The vessels were cleaned, cut into 1mm wide rings, and randomized into a control group with standard growth media, and 2 agonist groups (3nm, 10nm). Over 12 days, the length and number of new sprouts were recorded to assess the degree of penetration/perfusion and measure angiogenic activation, respectively. Statistical analysis included running a two-way ANOVA as well as recording the mean and standard deviation for sprout length and number.
RESULTS:
A significant increase in sprout length (pixel units) was observed 8 days onwards after the rings were exposed to the agonist compound at both the 10nm (196.21 ± 23.06) and 3nm (195.22 ± 38.90) concentrations when compared to control conditions (148.53 ± 27.98) (p< 0.01).
CONCLUSION:
This study provides pertinent information on TRPV4s role as a mediator for intracellular signalling where stimulation of the ion channel can potentially be a target for vascular remodelling and capillary growth, offering valuable insights into further research aimed at advancing cardiovascular function and exercise physiology. Current research in vivo is examining the synergistic potential between aerobic exercise and the TRPV4 cation channel on angiogenesis.