Cardiac remodeling is an adaptive, compensatory biological process following an initial insult to the myocardium that gradually becomes maladaptive and causes clinical deterioration and chronic heart failure (HF). This biological process involves several pathophysiological adaptations at the genetic, molecular, cellular, and tissue levels. A growing body of clinical and translational investigations demonstrated that cardiac remodeling and chronic HF does not invariably result in a static, end-stage phenotype but can be at least partially reversed. One of the paradigms which shed some additional light on the breadth and limits of myocardial elasticity and plasticity is long term mechanical circulatory support (MCS) in advanced HF pediatric and adult patients. MCS by providing (a) ventricular mechanical unloading and (b) effective hemodynamic support to the periphery results in functional, structural, cellular and molecular changes, known as cardiac reverse remodeling. Herein, we analyze and synthesize the advances in our understanding of the biology of MCS-mediated reverse remodeling and myocardial recovery. The MCS investigational setting offers access to human tissue, providing an unparalleled opportunity in cardiovascular medicine to perform in-depth characterizations of myocardial biology and the associated molecular, cellular, and structural recovery signatures. These human tissue findings have triggered and effectively fueled a “bedside to bench and back” approach through a variety of knockout, inhibition or overexpression mechanistic investigations in vitro and in vivo using small animal models. These follow-up translational and basic science studies leveraging human tissue findings have unveiled mechanistic myocardial recovery pathways which are currently undergoing further testing for potential therapeutic drug development. Essentially, the field is advancing by extending the lessons learned from the MCS cardiac recovery investigational setting to develop therapies applicable to the greater, not end-stage, HF population. This review article focuses on the biological aspects of the MCS-mediated myocardial recovery and together with its companion review article, focused on the clinical aspects, they aim to provide a useful framework for clinicians and investigators.

心脏重塑是心肌最初受到损伤后的一种适应性、代偿性生物过程，逐渐变得适应不良并导致临床恶化和慢性心力衰竭（HF）。这一生物过程涉及遗传、分子、细胞和组织水平上的多种病理生理适应。越来越多的临床和转化研究表明，心脏重塑和慢性心力衰竭并不一定会导致静态的终末期表型，但至少可以部分逆转。对晚期心力衰竭儿童和成人患者进行长期机械循环支持 (MCS) 是进一步阐明心肌弹性和可塑性的广度和局限性的范例之一。 MCS 通过向外周提供 (a) 心室机械卸载和 (b) 有效的血流动力学支持，导致功能、结构、细胞和分子变化，称为心脏逆重塑。在此，我们分析并综合了我们对 MCS 介导的逆重塑和心肌恢复的生物学理解的进展。 MCS 研究环境提供了接触人体组织的机会，为心血管医学领域提供了无与伦比的机会，可以深入表征心肌生物学以及相关的分子、细胞和结构恢复特征。这些人体组织发现通过使用小动物模型进行体外和体内的各种敲除、抑制或过度表达机制研究，触发并有效地推动了“床边到工作台和背部”的方法。 这些利用人体组织发现的后续转化和基础科学研究揭示了机械性心肌恢复途径，目前正在接受潜在治疗药物开发的进一步测试。从本质上讲，该领域正在通过扩展从 MCS 心脏恢复研究环境中吸取的经验教训来开发适用于更大而非终末期心力衰竭人群的疗法，从而取得进展。这篇综述文章重点关注 MCS 介导的心肌恢复的生物学方面，并与其配套综述文章重点关注临床方面，旨在为临床医生和研究人员提供有用的框架。