Company Five of Cadet Brigade, Third Military Medical University, Chongqing 400038, China.
Prog Biophys Mol Biol. 2013 Nov;113(2):284-8. doi: 10.1016/j.pbiomolbio.2013.07.004. Epub 2013 Jul 26.
Cardiac hypertrophy is a key risk factor for chronic heart failure. Current treatments predominantly focus on both reducing the peripheral vascular resistance and activating nerve-humoral system. However, these efforts can't reverse cardiac hypertrophy fundamentally. Ras association domain family 1 isoform A (RASSF1A) is a regulatory tumor suppressor whose inactivation by inappropriate promoter methylation has been implicated in the development of many human cancers. Recently, there have been a number of studies investigating the roles of RASSF1A in the pathophysiology of cardiac hypertrophy. In this review, we focus on the present progresses of cardiac RASSF1A under physiological and pathological conditions, trying to systematically elucidate how the RASSF1A-mediated signal pathways contribute to the maintenance of normal cardiac myocyte structure and function and lead to the regression of pathological cardiac hypertrophy. These pathways exert multiple functions such as regulating cardiac contractility, physiologically increasing stability of microtubule, preventing cardiac dysfunction, attenuating interstitial fibrosis and mediating cell apoptosis. These specific roles are highly relevant with cardiac hemodynamics and therapeutic strategies, indicating RASSF1A may have the potential to reverse pathological cardiac hypertrophy thus prevent heart failure fundamentally.
心肌肥厚是慢性心力衰竭的一个关键风险因素。目前的治疗方法主要集中在降低外周血管阻力和激活神经体液系统上。然而，这些努力并不能从根本上逆转心肌肥厚。Ras 相关结构域家族 1 成员 A（RASSF1A）是一种调节性肿瘤抑制因子，其启动子甲基化的失活与许多人类癌症的发展有关。最近，有许多研究探讨了 RASSF1A 在心肌肥厚病理生理学中的作用。在这篇综述中，我们重点介绍了生理和病理条件下心脏 RASSF1A 的现有进展，试图系统阐明 RASSF1A 介导的信号通路如何有助于维持正常心肌细胞的结构和功能，并导致病理性心肌肥厚的消退。这些途径具有多种功能，如调节心肌收缩力、生理性增加微管稳定性、防止心脏功能障碍、减轻间质纤维化和介导细胞凋亡。这些特定的作用与心脏血流动力学和治疗策略密切相关，表明 RASSF1A 可能具有逆转病理性心肌肥厚从而从根本上预防心力衰竭的潜力。
