Chung Charles S, Hiske Mark A, Chadha Arjun, Mueller Patrick J
Department of Physiology, Wayne State University, Detroit, MI, United States.
Front Physiol. 2020 Feb 5;11:15. doi: 10.3389/fphys.2020.00015. eCollection 2020.
A sedentary lifestyle is associated with increased cardiovascular risk factors and reduced cardiac compliance when compared to a lifestyle that includes exercise training. Exercise training increases cardiac compliance in humans, but the mechanisms underlying this improvement are unknown. A major determinant of cardiac compliance is the compliance of the giant elastic protein titin. Experimentally reducing titin compliance in animal models reduces exercise tolerance, but it is not known whether sedentary versus chronic exercise conditions cause differences in titin isoform content. We hypothesized that sedentary conditions would be associated with a reduction in the content of the longer, more compliant N2BA isoform relative to the stiffer N2B isoform (yielding a reduced N2BA:N2B ratio) compared to age-matched exercising controls. We obtained left ventricles from 16-week old rats housed for 12 weeks in standard (sedentary) or voluntary running wheel (exercised) housing. The N2BA:N2B ratio was decreased in the hearts of sedentary versus active rats ( = 0.041). Gene expression of a mRNA splicing factor, RNA Binding Motif 20 protein (RBM20), correlated negatively with N2BA:N2B ratios ( = 0.006, = -0.449), but was not different between groups, suggesting that RBM20 may be regulated post-transcriptionally. Total phosphorylation of cardiac titin was not different between the active and sedentary groups. This study is the first to demonstrate that sedentary rats exhibit reduced cardiac titin N2BA:N2B isoform ratios, which implies reduced cardiac compliance. These data suggest that a lack of exercise (running wheel) reduces cardiac compliance and that exercise itself increases cardiac compliance.
与包含运动训练的生活方式相比，久坐不动的生活方式与心血管危险因素增加和心脏顺应性降低有关。运动训练可提高人类的心脏顺应性，但其改善的潜在机制尚不清楚。心脏顺应性的一个主要决定因素是巨大弹性蛋白肌联蛋白的顺应性。在动物模型中通过实验降低肌联蛋白的顺应性会降低运动耐力，但尚不清楚久坐与长期运动条件是否会导致肌联蛋白异构体含量的差异。我们假设，与年龄匹配的运动对照组相比，久坐条件会导致较长、顺应性更高的N2BA异构体相对于较硬的N2B异构体含量降低（导致N2BA:N2B比值降低）。我们从16周龄的大鼠获取左心室，这些大鼠在标准（久坐）或自愿跑步轮（运动）环境中饲养12周。久坐大鼠与活跃大鼠心脏中的N2BA:N2B比值降低（P = 0.041）。一种mRNA剪接因子RNA结合基序20蛋白（RBM20）的基因表达与N2BA:N2B比值呈负相关（P = 0.006，r = -0.449），但两组之间无差异，这表明RBM20可能在转录后受到调控。活跃组和久坐组之间心脏肌联蛋白的总磷酸化没有差异。本研究首次表明，久坐大鼠的心脏肌联蛋白N2BA:N2B异构体比值降低，这意味着心脏顺应性降低。这些数据表明，缺乏运动（跑步轮）会降低心脏顺应性，而运动本身会增加心脏顺应性。
