Lalande Sophie, Mueller Patrick J, Chung Charles S
Department of Kinesiology & Health Education, The University of Texas at Austin, Austin, TX, USA.
Department of Physiology, Wayne State University, Detroit, MI, USA.
Exp Physiol. 2017 Sep 1;102(9):1055-1066. doi: 10.1113/EP086275. Epub 2017 Jul 31.
What is the topic of this review? This review focuses on how in vivo and molecular measurements of cardiac passive stiffness can predict exercise tolerance and how exercise training can reduce cardiac passive stiffness. What advances does it highlight? This review highlights advances in understanding the relationship between molecular (titin-based) and in vivo (left ventricular) passive stiffness, how passive stiffness modifies exercise tolerance, and how exercise training may be therapeutic for cardiac diseases with increased passive stiffness. Exercise can help alleviate the negative effects of cardiovascular disease and cardiovascular co-morbidities associated with sedentary behaviour; this may be especially true in diseases that are associated with increased left ventricular passive stiffness. In this review, we discuss the inverse relationship between exercise tolerance and cardiac passive stiffness. Passive stiffness is the physical property of cardiac muscle to produce a resistive force when stretched, which, in vivo, is measured using the left ventricular end diastolic pressure-volume relationship or is estimated using echocardiography. The giant elastic protein titin is the major contributor to passive stiffness at physiological muscle (sarcomere) lengths. Passive stiffness can be modified by altering titin isoform size or by post-translational modifications. In both human and animal models, increased left ventricular passive stiffness is associated with reduced exercise tolerance due to impaired diastolic filling, suggesting that increased passive stiffness predicts reduced exercise tolerance. At the same time, exercise training itself may induce both short- and long-term changes in titin-based passive stiffness, suggesting that exercise may be a treatment for diseases associated with increased passive stiffness. Direct modification of passive stiffness to improve exercise tolerance is a potential therapeutic approach. Titin passive stiffness itself may be a treatment target based on the recent discovery of RNA binding motif 20, which modifies titin isoform size and passive stiffness. Translating these discoveries that link exercise and left ventricular passive stiffness may provide new methods to enhance exercise tolerance and treat patients with cardiovascular disease.
这篇综述的主题是什么？本综述聚焦于心脏被动僵硬度的体内和分子测量如何预测运动耐量，以及运动训练如何降低心脏被动僵硬度。它突出了哪些进展？本综述突出了在理解分子（基于肌联蛋白的）和体内（左心室）被动僵硬度之间的关系、被动僵硬度如何改变运动耐量，以及运动训练如何对具有增加的被动僵硬度的心脏疾病具有治疗作用方面的进展。运动有助于减轻心血管疾病以及与久坐行为相关的心血管合并症的负面影响；在与左心室被动僵硬度增加相关的疾病中可能尤其如此。在本综述中，我们讨论了运动耐量与心脏被动僵硬度之间的反比关系。被动僵硬度是心肌在被拉伸时产生阻力的物理特性，在体内，它是通过左心室舒张末期压力-容积关系来测量的，或者是通过超声心动图来估计的。巨大的弹性蛋白肌联蛋白是生理肌肉（肌节）长度下被动僵硬度的主要贡献者。被动僵硬度可以通过改变肌联蛋白异构体大小或通过翻译后修饰来改变。在人类和动物模型中，左心室被动僵硬度增加与由于舒张期充盈受损导致的运动耐量降低相关，这表明被动僵硬度增加预示着运动耐量降低。同时，运动训练本身可能会引起基于肌联蛋白的被动僵硬度的短期和长期变化，这表明运动可能是治疗与被动僵硬度增加相关疾病的一种方法。直接改变被动僵硬度以提高运动耐量是一种潜在的治疗方法。基于最近发现的RNA结合基序20，肌联蛋白被动僵硬度本身可能是一个治疗靶点，该基序可改变肌联蛋白异构体大小和被动僵硬度。将这些将运动与左心室被动僵硬度联系起来的发现进行转化，可能会提供增强运动耐量和治疗心血管疾病患者的新方法。
