Non-coding RNAs as therapeutic targets for preventing myocardial ischemia-reperfusion injury

ABSTRACT

Introduction: New treatments are required to improve clinical outcomes in patients with acute myocardial infarction (AMI), for reduction of myocardial infarct (MI) size and preventing heart failure. Following AMI, acute ischemia/reperfusion injury (IRI) ensues, resulting in cardiomyocyte death and impaired cardiac function. Emerging studies have implicated a fundamental role for non-coding RNAs (microRNAs [miRNA], and more recently long non-coding RNAs [lncRNA]) in the setting of acute myocardial IRI.

Areas covered: In this article, we discuss the roles of miRNAs and lncRNAs as potential biomarkers and therapeutic targets for the detection and treatment of AMI, review their roles as mediators and effectors of cardioprotection, particularly in the settings of interventions such as ischemic pre- and post-conditioning (IPC & IPost) as well as remote ischemic conditioning (RIC), and highlight future strategies for targeting ncRNAs to reduce MI size and prevent heart failure following AMI.

Expert opinion: Investigating the roles of miRNAs and lncRNAs in the setting of AMI has provided new insights into the pathophysiology underlying acute myocardial IRI, and has identified novel biomarkers and therapeutic targets for detecting and treating AMI. Pharmacological and genetic manipulation of these ncRNAs has the therapeutic potential to improve clinical outcomes in AMI patients.

KEYWORDS:

• Ischemia-reperfusion injury
• long non-coding RNA
• microRNAs
• non-coding RNAs
• acute myocardial infarction
• cardioprotection
• ischemic conditioning

Article highlights

• Once considered ‘genomic junk’, non-coding regions of the genome are shown to produce ncRNAs which play critical roles in the regulation of cardiac development and cardiac diseases such as left ventricular hypertrophy, heart failure, and acute myocardial infarction.

• Both miRNAs and lncRNAs play important role in the pathogenesis of acute myocardial ischemia-reperfusion injury.

• Modulation of miRNAs and lncRNAs provides a potential therapeutic strategy for cardioprotection.

• Emerging evidence supports the existence of cross-talk between miRNAs and lncRNAs that regulate distinct molecular events during acute myocardial IRI.

This box summarizes key points contained in the article.

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. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

SB Ong is supported by the Singapore Ministry of Health’s National Medical Research Council under its Open Fund-Young Individual Research Grant (OF-YIRG) – NMRC/OFYIRG/0021/2016 as well as a Khoo Postdoctoral Fellowship Award (KPFA) – Duke-NUS-KPFA/2016/0010 from the Estate of Tan Sri Khoo Teck Puat, Singapore. SG Ong is supported by a National Institutes of Health Pathway to Independence Award K99HL130416. DJ Hausenloy is supported by the British Heart Foundation [FS/10/039/28270]; Duke-National University Singapore Medical School; Singapore Ministry of Health’s National Medical Research Council under its Clinician Scientist-Senior Investigator scheme [NMRC/CSA-SI/0011/2017] and Collaborative Centre Grant scheme [NMRC/CGAug16C006]; and the Singapore Ministry of Education Academic Research Fund Tier 2 [MOE2016-T2-2-021].