Regression of pathological cardiac hypertrophy: signaling pathways and therapeutic targets.
Regression of pathological cardiac hypertrophy: signaling pathways and therapeutic targets.
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DOI：
10.1016/j.pharmthera.2012.06.006
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发表时间：
2012-09
影响因子：
13.5
通讯作者：
Kang, Y. James
中科院分区：
文献类型：
--
作者：
Hou, Jianglong;Kang, Y. James
病理性心肌肥厚是心力衰竭的关键危险因素。它与间质纤维化、细胞死亡和心功能不全有关。长期以来，病理性心肌肥厚的进展被认为是不可逆转的。然而，最近的临床观察和实验研究表明，病理性心肌肥厚是可以逆转的。左心辅助装置用于心力衰竭患者的移植桥接，不仅改善了外周循环，而且往往会导致心脏几何形状的反向重塑和心脏功能的恢复。补充生理水平的铜可以逆转小鼠的病理性心肌肥厚。血管生成是必不可少的，而血管内皮生长因子(VEGF)是其消退的一个结构性因素。血管内皮生长因子的作用由血管内皮生长因子受体-1介导，其激活与环状GMP依赖的蛋白激酶-1(PKG-1)信号通路有关，抑制环状GMP的降解导致病理性心肌肥厚的消退。这些通路大多受低氧诱导因子的调控。促进血管生成的潜在治疗靶点包括：促进血管生成，选择性增强血管内皮生长因子受体-1信号通路，刺激PKG-1通路，抑制低氧诱导因子转录活性。关于病理性心肌肥厚消退的更多令人兴奋的见解正在浮现。将病理性心肌肥厚消退的概念转化为临床实践的时代即将到来。
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.
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影响因子：
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作者：
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