Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, China.
Pharmacol Ther. 2012 Sep;135(3):337-54. doi: 10.1016/j.pharmthera.2012.06.006. Epub 2012 Jun 29.
Pathological cardiac hypertrophy is a key risk factor for heart failure. It is associated with increased interstitial fibrosis, cell death and cardiac dysfunction. The progression of pathological cardiac hypertrophy has long been considered as irreversible. However, recent clinical observations and experimental studies have produced evidence showing the reversal of pathological cardiac hypertrophy. Left ventricle assist devices used in heart failure patients for bridging to transplantation not only improve peripheral circulation but also often cause reverse remodeling of the geometry and recovery of the function of the heart. Dietary supplementation with physiologically relevant levels of copper can reverse pathological cardiac hypertrophy in mice. Angiogenesis is essential and vascular endothelial growth factor (VEGF) is a constitutive factor for the regression. The action of VEGF is mediated by VEGF receptor-1, whose activation is linked to cyclic GMP-dependent protein kinase-1 (PKG-1) signaling pathways, and inhibition of cyclic GMP degradation leads to regression of pathological cardiac hypertrophy. Most of these pathways are regulated by hypoxia-inducible factor. Potential therapeutic targets for promoting the regression include: promotion of angiogenesis, selective enhancement of VEGF receptor-1 signaling pathways, stimulation of PKG-1 pathways, and sustention of hypoxia-inducible factor transcriptional activity. More exciting insights into the regression of pathological cardiac hypertrophy are emerging. The time of translating the concept of regression of pathological cardiac hypertrophy to clinical practice is coming.
病理性心肌肥厚是心力衰竭的一个关键风险因素。它与间质纤维化、细胞死亡和心脏功能障碍的增加有关。病理性心肌肥厚的进展长期以来被认为是不可逆转的。然而，最近的临床观察和实验研究提供了证据，表明病理性心肌肥厚可以逆转。心力衰竭患者用于桥接移植的左心室辅助装置不仅改善了外周循环，而且常常导致心脏几何形状的反向重构和功能的恢复。用生理相关水平的铜进行饮食补充可以使小鼠的病理性心肌肥厚逆转。血管生成是必不可少的，血管内皮生长因子（VEGF）是其退化的组成性因子。VEGF 的作用是通过 VEGF 受体-1 介导的，其激活与环鸟苷酸依赖性蛋白激酶-1（PKG-1）信号通路有关，抑制环鸟苷酸的降解导致病理性心肌肥厚的逆转。这些通路大多受缺氧诱导因子调节。促进逆转的潜在治疗靶点包括：促进血管生成、选择性增强 VEGF 受体-1 信号通路、刺激 PKG-1 通路和维持缺氧诱导因子转录活性。病理性心肌肥厚逆转的研究有了更多令人兴奋的新见解。将病理性心肌肥厚逆转的概念转化为临床实践的时机已经到来。
