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

ABSTRACT

Introduction: 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.

KEYWORDS:

• AntagomiR
• β-adrenergic balance
• ERK1/2 pathway
• GSK3
• heart failure
• microRNAs
• relaxin
• TWEAK/fn14 axis

Article highlights

• Some receptor mediated signaling pathways and micro-RNAs have potential as candidate target pathways in pathogenesis of heart failure.

• Most of signaling pathway implicated in cardiac hypertrophy operate through phosphorylation/dephosphorylation processes.

• Over the last few years several studies have reported the role of Glycogen synthase kinase 3 (GSK3).

• Several miRNAs have been reported as involved in pathogenesis of heart failure and MiR-1 is likely one of the most abundant microRNAs expressed in the heart and it was described in cardiac and skeletal muscle and its role in cardiac differentiation was also reported.

• MAP kinase has been found to be implicated in hypertrophic and heart failure and several studies have reported a negative effect of ERK1/2 signaling in human heart function.

• The increase in beta AR signaling has toxic cardiac effects and the different role of β₁ AR and β₂AR on cardiomyocyte survival and death is related to their distinct G protein coupling.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded