Fedak Paul W M, Verma Subodh, Weisel Richard D, Li Ren-Ke
Division of Cardiac Surgery, Toronto General Hospital, University of Toronto, 14EN-215, 200 Elizabeth Street, Toronto, ON, Canada M5G 2C4.
Cardiovasc Pathol. 2005 Jan-Feb;14(1):1-11. doi: 10.1016/j.carpath.2004.12.002.
The process of heart failure appears to be a common and coordinated response to cardiac injury and dysfunction. The contemporary mechanistic viewpoint that predictable, shared, highly regulated events underlie the complex heart failure process implies that an improved understanding of these mechanisms is fundamental to the advancement of cardiovascular biology and the subsequent development of targeted, effective treatment strategies for patients with congestive heart failure (CHF). Cardiac remodeling (CR) is the restructuring and reshaping of the heart that underlies heart failure progression. CR is a major determinant of the clinical course of CHF, irrespective of its etiology. The traditional concepts of cellular remodeling in the failing heart are based on well-established data indicating characteristic alterations in cell size, shape, and the ability to perform contractile work. The role of programmed cell death and the exciting possibility of cardiomyocyte regeneration are areas of intense investigation. Notably, the accumulating data in both animal and human hearts suggesting cardiomyocyte regeneration and renewal indicate that cellular remodeling is a complex and dynamic process that is not completely understood. For the development of new treatments to regenerate and restore failing myocardium, the possibilities offered by controlling cell death and enhancing cell renewal as a therapeutic target are unprecedented. Based on a critical review of the available literature, the traditional concepts and mechanisms describing the regulation of remodeling are largely inadequate. The neurohormonal (RAAS and adrenergic systems) and innovative cytokine hypothesis (TNF-alpha and others) of remodeling and failure do not account for all the cellular and molecular changes that result in the progression of CHF. Given that these contemporary concepts serve as the basis for the majority of our current heart failure treatments, it is not surprising that CHF is an emerging epidemic in our society. To define new therapeutic targets and to control the process of remodeling, novel biomolecules and mechanisms for the coordinated control of CR must be further defined.
心力衰竭的过程似乎是对心脏损伤和功能障碍的一种常见且协调的反应。当代的机制观点认为，可预测、共享且高度 regulated 的事件是复杂心力衰竭过程的基础，这意味着更好地理解这些机制对于心血管生物学的进展以及随后为充血性心力衰竭（CHF）患者制定有针对性的有效治疗策略至关重要。心脏重塑（CR）是心力衰竭进展背后的心脏结构和形态的重塑。CR 是 CHF 临床病程的主要决定因素，无论其病因如何。衰竭心脏中细胞重塑的传统概念基于已确立的数据，这些数据表明细胞大小、形状以及进行收缩工作的能力发生了特征性改变。程序性细胞死亡的作用以及心肌细胞再生这一令人兴奋的可能性是深入研究的领域。值得注意的是，动物和人类心脏中积累的数据表明心肌细胞再生和更新，这表明细胞重塑是一个复杂且动态的过程，尚未完全被理解。对于开发用于再生和恢复衰竭心肌的新疗法而言，将控制细胞死亡和增强细胞更新作为治疗靶点所提供的可能性是前所未有的。基于对现有文献的批判性综述，描述重塑调节的传统概念和机制在很大程度上是不充分的。重塑和衰竭的神经激素（RAAS 和肾上腺素能系统）以及创新性细胞因子假说（TNF-α 等）并不能解释导致 CHF 进展的所有细胞和分子变化。鉴于这些当代概念是我们当前大多数心力衰竭治疗的基础，CHF 在我们社会中成为一种新兴流行病也就不足为奇了。为了确定新的治疗靶点并控制重塑过程，必须进一步明确用于协调控制 CR 的新型生物分子和机制。
