JSS College of Pharmacy(1) (Off campus of JSS University, Mysore), Ooty, Tamilnadu, India. ahuja
Pharmacol Res. 2010 Apr;61(4):269-80. doi: 10.1016/j.phrs.2009.11.012. Epub 2009 Dec 5.
Cardiac hypertrophy is one of the main ways in which cardiomyocytes respond to mechanical and neurohormonal stimuli. It enables myocytes to increase their work output, which improves cardiac pump function. Although cardiac hypertrophy may initially represent an adaptive response of the myocardium, ultimately, it often progresses to ventricular dilatation and heart failure which is one of the leading causes of mortality in the western world. A number of signaling modulators that influence gene expression, apoptosis, cytokine release and growth factor signaling, etc. are known to regulate heart. By using genetic and cellular models of cardiac hypertrophy it has been proved that pathological hypertrophy can be prevented or reversed. This finding has promoted an enormous drive to identify novel and specific regulators of hypertrophy. In this review, we have discussed the various molecular signal transduction pathways and the regulators of hypertrophic response which includes calcineurin, cGMP, NFAT, natriuretic peptides, histone deacetylase, IL-6 cytokine family, Gq/G11 signaling, PI3K, MAPK pathways, Na/H exchanger, RAS, polypeptide growth factors, ANP, NO, TNF-alpha, PPAR and JAK/STAT pathway, microRNA, Cardiac angiogenesis and gene mutations in adult heart. Augmented knowledge of these signaling pathways and their interactions may potentially be translated into pharmacological therapies for the treatment of various cardiac diseases that are adversely affected by hypertrophy. The purpose of this review is to provide the current knowledge about the molecular pathogenesis of cardiac hypertrophy, with special emphasis on novel researches and investigations.
心肌肥厚是心肌细胞对机械和神经激素刺激的主要反应方式之一。它使心肌细胞能够增加其工作量，从而改善心脏泵功能。虽然心肌肥厚最初可能代表心肌的适应性反应，但最终它通常会进展为心室扩张和心力衰竭，这是西方世界主要的死亡原因之一。许多信号调节剂，如影响基因表达、细胞凋亡、细胞因子释放和生长因子信号等，已知可调节心脏。通过使用心肌肥厚的遗传和细胞模型，已经证明病理性肥厚可以预防或逆转。这一发现极大地推动了寻找新的和特异性的肥厚调节剂的努力。在这篇综述中，我们讨论了各种分子信号转导途径和肥厚反应的调节剂，包括钙调神经磷酸酶、cGMP、NFAT、利钠肽、组蛋白去乙酰化酶、IL-6 细胞因子家族、Gq/G11 信号、PI3K、MAPK 途径、Na/H 交换体、RAS、多肽生长因子、ANP、NO、TNF-α、PPAR 和 JAK/STAT 途径、miRNA、心脏血管生成和成人心脏中的基因突变。对这些信号通路及其相互作用的认识的增强，可能会转化为治疗各种受肥厚影响的心脏疾病的药理学治疗方法。本综述的目的是提供心肌肥厚的分子发病机制的最新知识，特别强调新的研究和调查。
