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微小 RNA 和受体介导的信号通路作为心力衰竭的潜在治疗靶点。

MicroRNA and receptor mediated signaling pathways as potential therapeutic targets in heart failure.

机构信息

a U.O.C di Medicina Interna con Stroke Care, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S) , University of Palermo , Palermo , Italy.

出版信息

Expert Opin Ther Targets. 2016 Nov;20(11):1287-1300. doi: 10.1080/14728222.2016.1212017. Epub 2016 Jul 25.

Abstract

Cardiac remodelling is a complex pathogenetic pathway involving genome expression, molecular, cellular, and interstitial changes that cause changes in size, shape and function of the heart after cardiac injury. Areas covered: We will review recent advances in understanding the role of several receptor-mediated signaling pathways and micro-RNAs, in addition to their potential as candidate target pathways in the pathogenesis of heart failure. The myocyte is the main target cell involved in the remodelling process via ischemia, cell necrosis and apoptosis (by means of various receptor pathways), and other mechanisms mediated by micro-RNAs. We will analyze the role of some receptor mediated signaling pathways such as natriuretic peptides, mediators of glycogen synthase kinase 3 and ERK1/2 pathways, beta-adrenergic receptor subtypes and relaxin receptor signaling mechanisms, TNF/TNF receptor family and TWEAK/Fn14 axis, and some micro-RNAs as candidate target pathways in pathogenesis of heart failure. These mediators of receptor-mediated pathways and micro-RNA are the most addressed targets of emerging therapies in modern heart failure treatment strategies. Expert opinion: Future treatment strategies should address mediators involved in multiple steps within heart failure pathogenetic pathways.

摘要

心脏重构是一个涉及基因组表达、分子、细胞和间质变化的复杂病理途径,它会导致心脏损伤后心脏的大小、形状和功能发生变化。

涵盖领域

我们将回顾近年来在理解几种受体介导的信号通路和 microRNA 的作用方面的进展,以及它们作为心力衰竭发病机制中候选靶向通路的潜力。心肌细胞是通过缺血、细胞坏死和细胞凋亡(通过各种受体通路)以及 microRNA 介导的其他机制参与重构过程的主要靶细胞。我们将分析一些受体介导的信号通路的作用,如利钠肽、糖原合酶激酶 3 和 ERK1/2 通路的调节剂、β-肾上腺素能受体亚型和松弛素受体信号机制、TNF/TNF 受体家族和 TWEAK/Fn14 轴,以及一些 microRNA 作为心力衰竭发病机制中的候选靶向通路。这些受体介导的通路和 microRNA 的介质是现代心力衰竭治疗策略中新兴治疗方法的最主要靶点。

专家意见

未来的治疗策略应该针对心力衰竭发病机制途径中的多个步骤涉及的介质。

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