LAUSR

Background: Chronic exercise protocols have demonstrated a beneficial effect on overall cardiovascular health, however, the direct effects on left ventricular (LV) function and the relation to changes in post-transcriptional regulatory checkpoints, that is the microRNAs (miRs), and what downstream processes may be affected, remains unexplored. Accordingly, this study developed a chronic exercise protocol in mature pigs and examined LV function and myocardial mRNA profiles. Methods and Results: Pigs (n=9; 25 Kg) underwent a treadmill protocol (4 weeks, 10° elevation, 2.5 mph, 10 minutes) in which LV ejection fraction (LV EF) and end-diastolic volume (LV EDV) were measured by echocardiography. Age matched, non-exercise pigs (n=6) served as referent controls. LV myocardial samples were subjected to an 84 miR array using rt-PCR. All results are reported as mean ± SEM. LV EDV (54.8 ± 3.1 vs 67.4 ± 3.3 mL, p≤0.05) and LV EF (66.4 ± 1.8 vs 82.0 ± 0.7 %, p≤0.05) increased with exercise indicative of a successful training effect. A total of 25 miRs were significantly upregulated (56%) or downregulated (44%) following exercise. Using miR mapping algorithms, miR-22 and miR-30e, which fell by over 3-fold change with exercise (rt-PCR, -3.07 ± 0.92 and -3.28 ± 1.08 respectively, p≤0.05), mapped to the NLRP3 inflammasome. NLRP-3 mRNA (rt-PCR) levels fell by over 2-fold with exercise (-2.65 ± 0.62, p≤0.05). Conclusion: A chronic exercise protocol in pigs induced a unique miR profile that was associated with changes in LV geometry and function. In particular, several miRs mapped to regulatory elements of the local inflammatory pathway- the inflammasome. These unique findings demonstrated a clear shift in post-transcriptional pathways occur with chronic exercise and reduces LV myocardial inflammasome profiles. 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.