Progress in neuregulin/ErbB signaling and chronic heart failure

• 作者: Hong-Kun Yin Ming-Dong Zhou Xin-Yan Li Zheng-Gang Jiang
• 来源期刊: 世界高血压杂志
• 学科: 医学
• 关键词: ERBB EPIGENETIC modification HEART failure METABOLISM NEUREGULIN-1
• 年，卷（期）: 2015,（2）
• 页码范围: 63-73
• 页数: 11页
• 分类号: R

摘要

Heart failure is one of the leading causes of death today.It is a complex clinical syndrome in which the heart has a reduced contraction ability and decreased viable myocytes.Novel approaches to the clinical management of heart failure have been achieved through an understanding of the molecular pathways necessary for normal heart development.Neuregulin-1(NRG-1)has emerged as a potential therapeutic target based on the fact that mice null for NRG-1 or receptors mediating its activity,ErbB2 and ErbB4,are embryonic lethal and exhibit severe cardiac defects.Preclinical studies performed with animal models of heart failure demonstrate that treatment with NRG-1 significantly improves heart function and survival.Clinical data further support NRG-1 as a promising drug candidate for the treatment of cardiac dysfunction in patients.Recent studies have revealed the mechanism underlying the therapeutic effects of NRG-1/ErbB signaling in the treatment of heart failure.Through activation of upstream signaling molecules such as phosphoinositide 3-kinase,mitogen-activated protein kinase,and focal adhesion kinase,NRG-1/ErbB pathway activation results in increased cMLCK expression and enhanced intracellular calcium cycling.The former is a regulator of the contractile machinery,and the latter triggers cell contraction and relaxation.In addition,NRG-1/ErbB signaling also influences energy metabolism and induces epigenetic modification in cardiac myocytes in a way that more closely resembles healthy heart.These observations reveal potentially new treatment options for heart failure.