Author(s): MALKA, G., BERGDAHL, A., Institution: CONCORDIA UNIVERSITY , Country: CANADA, Abstract-ID: 1668

INTRODUCTION:
Angiogenesis (ANG), the formation of new capillaries, is essential for microcirculatory adaptations. Capillaries represent the terminal site for oxygen diffusion and metabolite clearance in active skeletal muscle (SKM). Exercise drives ANG through mechanical stimuli, thereby enhancing cardiovascular hemodynamics and muscle fibre capillarization. Skeletal muscle is a highly adaptive tissue, modifying its size in response to various stimuli, including increased oxygen supply. Augmenting ANG remains a crucial target for enhancing endurance performance, SKM growth, and recovery in recreationally active populations and well-trained endurance athletes. The Transient Receptor Potential Vanilloid 4 (TRPV4) channel is moderately permeable to Ca2+ and is highly expressed in vascular endothelial cells, regulating several cellular processes, including cell proliferation and migration. Activation of TRPV4 via a selective agonist (GSK1016790) has not been extensively studied. We hypothesized that TRPV4 activation would increase the angiogenic and aerobic benefits of moderate-intensity continuous training (MICT), enhancing functional aerobic capacity (FAC) and SKM fiber cross-sectional area (CSA).
METHODS:
Two- to three-month-old C57Bl/6 mice were randomized into four groups: control, GSK treatment, exercise only (EXCI), and combined GSK plus exercise (GSK+). Exercise groups underwent 6 weeks of MICT on a treadmill, 4 days/week, after 2 weeks of acclimation. Baseline FAC was assessed using a maximal aerobic capacity ramp test (MAC) and was repeated bi-weekly to adjust training load. Intensity started at 60% of MAC for 40 minutes, with increments of 5% MAC and five minutes in duration. Following the 8-week intervention, frozen vastus lateralis SKM tissue was sliced with a cryostat into 14µm sections, followed by histology with a hematoxylin and eosin stain. Sections were imaged using a Leica inverted microscope connected to a camera, and CSA was measured using AmLite software.
RESULTS:
Findings indicated significantly greater MAC treadmill speed (m/min) in the GSK+ and EXCI groups across all time points after the baseline (34.0±0.97, 36.33±1.05), (weeks 2 (37.3 ±0.97, 37.3±0.97) (p=0.001, p=0.002); 4 (37.0±1.05, 37.3±1.20) (p<0.001), and 6 (38.3±0.75, 36.0±1.63) (p<0.001, p=0.002)) compared to control (32.0±0.74, 29.0±1.12, 28.3±0.56, 27.6±0.57). Additionally, the GSK, EXCI and GSK+ groups showed significantly greater mean CSA (µm^2) (1658.79±12.85, 1749.93±14.98, 1795.70±12.03 ; p<0.001) compared to control (1553.70±17.14). Interestingly, GSK+ also showed significance when compared to EXCI (p=0.023).
CONCLUSION:
This study demonstrates that MICT coupled with TRPV4 activation can be a target for vascular remodelling, offering valuable insights to advance cardiovascular function, endurance performance, and muscle hypertrophy. Current research aims to solidify the findings by analyzing capillary density via capillary staining and detecting specific angiogenic growth factors via immunoblotting.