Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC, United States of America.
Columbia VA Health Care System, Columbia, SC, United States of America.
PLoS One. 2024 Feb 2;19(2):e0292243. doi: 10.1371/journal.pone.0292243. eCollection 2024.
Standardized exercise protocols have been shown to improve overall cardiovascular fitness, but direct effects on left ventricular (LV) function, particularly diastolic function and relation to post-transcriptional molecular pathways (microRNAs (miRs)) are poorly understood. This project tested the central hypothesis that adaptive LV remodeling resulting from a large animal exercise training protocol, would be directly associated with specific miRs responsible for regulating pathways relevant to LV myocardial stiffness and geometry.
Pigs (n = 9; 25 Kg) underwent a 4 week exercise training protocol (10 degrees elevation, 2.5 mph, 10 min, 5 days/week) whereby LV chamber stiffness (KC) and regional myocardial stiffness (rKm) were measured by Doppler/speckle tracking echocardiography. Age and weight matched non-exercise pigs (n = 6) served as controls. LV KC fell by approximately 50% and rKm by 30% following exercise (both p < 0.05). Using an 84 miR array, 34 (40%) miRs changed with exercise, whereby 8 of the changed miRs (miR-19a, miR-22, miR-30e, miR-99a, miR-142, miR-144, miR-199a, and miR-497) were correlated to the change in KC (r ≥ 0.5 p < 0.05) and mapped to matrix and calcium handling processes. Additionally, miR-22 and miR-30e decreased with exercise and mapped to a localized inflammatory process, the inflammasome (NLRP-3, whereby a 2-fold decrease in NLRP-3 mRNA occurred with exercise (p < 0.05).
Chronic exercise reduced LV chamber and myocardial stiffness and was correlated to miRs that map to myocardial relaxation processes as well as local inflammatory pathways. These unique findings set the stage for utilization of myocardial miR profiling to identify underlying mechanisms by which exercise causes changes in LV myocardial structure and function.
标准化的运动方案已被证明可以提高整体心血管健康水平，但对于左心室（LV）功能的直接影响，特别是舒张功能以及与转录后分子途径（microRNAs（miRs））的关系，了解甚少。本项目测试了一个中心假设，即来自大型动物运动训练方案的适应性 LV 重塑将与负责调节与 LV 心肌僵硬度和几何形状相关途径的特定 miR 直接相关。
猪（n=9；25 公斤）进行了为期 4 周的运动训练方案（10 度倾斜，2.5 英里/小时，10 分钟，每周 5 天），通过多普勒/斑点跟踪超声心动图测量 LV 腔室僵硬度（KC）和局部心肌僵硬度（rKm）。年龄和体重匹配的非运动猪（n=6）作为对照组。运动后 LV KC 下降约 50%，rKm 下降约 30%（均 p<0.05）。使用 84 个 miR 阵列，有 34 个（40%）miRs 随运动而变化，其中 8 个变化的 miR（miR-19a、miR-22、miR-30e、miR-99a、miR-142、miR-144、miR-199a 和 miR-497）与 KC 的变化相关（r≥0.5，p<0.05），并映射到基质和钙处理过程。此外，miR-22 和 miR-30e 随运动而减少，并映射到局部炎症过程，即炎症小体（NLRP-3），其中 NLRP-3 mRNA 在运动时减少了 2 倍（p<0.05）。
慢性运动降低了 LV 腔室和心肌僵硬度，与 miR 相关，这些 miR 映射到心肌松弛过程以及局部炎症途径。这些独特的发现为利用心肌 miR 谱分析来确定运动引起 LV 心肌结构和功能变化的潜在机制奠定了基础。
