Left ventricle function and post-transcriptional events with exercise training in pigs.

Left ventricle function and post-transcriptional events with exercise training in pigs.
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DOI:
10.1371/journal.pone.0292243
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发表时间:
2024
期刊:
影响因子:
3.7
通讯作者:
--
中科院分区:
综合性期刊3区
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--
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标准化运动方案已被证明可以改善整体心血管健康,但对左心室(LV)功能的直接影响,特别是舒张功能以及与转录后分子通路(microRNA(miR))的关系知之甚少。该项目测试了中心假设,即由大型动物运动训练方案引起的适应性LV重构将与负责调节与LV心肌硬度和几何形状相关的通路的特定miR直接相关。猪(n = 9; 25 Kg)进行4周运动训练方案(10度升高,2.5mph,10分钟,5天/周),由此通过多普勒/斑点跟踪超声心动图测量LV腔室硬度(KC)和局部心肌硬度(rKm)。年龄和体重匹配的非运动猪(n = 6)作为对照。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,34个(40%)miR随着运动而改变,其中8个改变的miR(miR-19 a、miR-22、miR-30 e、miR-99 a、miR-142、miR-144、miR-199 a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-30 e随着运动而减少,并映射到局部炎症过程,即炎性小体(NLRP-3),其中NLRP-3 mRNA随着运动发生2倍减少(p < 0.05)。慢性运动降低了LV腔和心肌硬度,并与心肌舒张过程以及局部炎症通路的miR相关。这些独特的发现为利用心肌miR谱确定运动引起LV心肌结构和功能变化的潜在机制奠定了基础。
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.
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