Relation between left ventricular relaxation and post-transcriptional regulation with exercise in pigs

Abstract

Background: Regular exercise has been shown to induce physiological adaptations such as improved left ventricle (LV) function, but LV diastolic function, particularly LV chamber stiffness (LV Kc) is rarely examined. In addition, the relation between changes in LV function, particularly LV Kc with regular exercise and post-transcriptional regulator checkpoints, the microRNAs (miRs), remains unexplored. This project tested the hypothesis that an exercise protocol in pigs will cause a shift in miR profiles which would affect pathways relevant to LV Kc. Methods and Results: Pigs (n=9; 3 months) underwent a chronic treadmill protocol (4 weeks, 10° elevation, 2.5 mph, 10 minutes) and two-dimensional speckle-tracking echocardiography was performed to obtain LV ejection fraction (LV EF) and to compute LV Kc. Age and weight matched non-exercised pigs (n=6) served as referent controls. All results are reported as mean ± SEM. LV EF increased with exercise (66.7 ± 1.9 vs 82.0 ± 0.7 %, p≤0.05) whereas LV Kc fell by approximately 50% (0.56 ± 0.04 vs 0.27 ± 0.02 kPa, p≤0.05). Using an 84 miR array (rt-PCR), a total of 34 (40%) miRs changed with exercise whereas 8 miRs (miR-19a, miR-22, miR-30e, miR-99a, miR-142, miR-144, miR-199a, and miR-497) correlated to LV Kc (r= 0.543, r=0.646, r=0.671, r=0.638, r=0.814, r=0.613, r=0.575, r=0.726 respectively, p≤0.05). Specifically, these miRs mapped to functional domains relevant to LV Kc such as calcium handling/active relaxation and extracellular matrix remodeling (i.e. metallopeptidases, heparin sulfate proteoglycans, and transforming growth factor-beta). Conclusion: Chronic exercise in pigs reduced LV chamber stiffness and correlated to miRs that mapped to regulatory processes which likely contributed to this reduction. Thus, utilization of miR profiling may provide insight into exercise training effectiveness. This work was supported in part by National Institutes of Health grant R01HL130972-01A1 (F.G.S.) & R01HL5949 (F.G.S.) as well as a Merit Award from the Veterans Health Administration, BX000168-10A1 (F.G.S.) & BX005320 (F.G.S.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.