Non-Coding RNAs: Prevention, Diagnosis, and Treatment in Myocardial Ischemia–Reperfusion Injury

Abstract

Recent knowledge concerning the role of non-coding RNAs (ncRNAs) in myocardial ischemia/reperfusion (I/R) injury provides new insight into their possible roles as specific biomarkers for early diagnosis, prognosis, and treatment. MicroRNAs (miRNAs) have fewer than 200 nucleotides, while long ncRNAs (lncRNAs) have more than 200 nucleotides. The three types of ncRNAs (miRNAs, lncRNAs, and circRNAs) act as signaling molecules strongly involved in cardiovascular disorders (CVD). I/R injury of the heart is the main CVD correlated with acute myocardial infarction (AMI), cardiac surgery, and transplantation. The expression levels of many ncRNAs and miRNAs are highly modified in the plasma of MI patients, and thus they have the potential to diagnose and treat MI. Cardiomyocyte and endothelial cell death is the major trigger for myocardial ischemia–reperfusion syndrome (MIRS). The cardioprotective effect of inflammasome activation in MIRS and the therapeutics targeting the reparative response could prevent progressive post-infarction heart failure. Moreover, the pharmacological and genetic modulation of these ncRNAs has the therapeutic potential to improve clinical outcomes in AMI patients.

Circular RNAs: Biogenesis, Biological Functions, and Roles in Myocardial Infarction

“…Vausort et al [ 89 ] identified circRNA MICRA connected with MI in peripheral blood and discovered that low MICRA levels are typical of MI and deteriorate left heart function. Cuimei Zhao et al [ 90 ] employed a circRNA array to detect the expression level of circRNA in coronary blood samples from MI patients and normal subjects. In the blood of the MI patients, Hsa_circRNA_001654 and hsa_circRNA_091761 were significantly increased, as observed in differential expression analyses, enabling them to act as a potential biomarker for the early diagnosis of MI.…”

The Role of ncRNAs in Cardiac Infarction and Regeneration

“…The molecular bases that govern cardiac regeneration are very complex, including both coding RNAs and non-coding RNAs (ncRNAs) as pivotal modulators. Researchers began addressing the impacts of non-coding RNAs some years ago, and it was through such research that it was discovered that they are powerful regulators of a multitude of cellular and pathological processes such as MI, hypertrophy, HF, and arrhythmias [ 27 ]. ncRNAs are functional RNA molecules (without protein-coding functions) that play an essential role in distinct biological and physiological processes as well as pathological disorders [ 28 ].…”

Mechanism of heart failure after myocardial infarction

“…63 Epigenetic regulation of non-coding RNAs, including long-stranded non-coding RNAs and microRNAs, play an essential role in I/R injury through endoplasmic reticulum (ER)–mitochondria microdomain interactions. 64 The sensitivity of CMs to death is fine-tuned by the intracellular calcium concentration. Therefore, when inositol 1,4,5-trisphosphate receptor (IP3R)-mediated I/R stress upregulates and leads to mitochondrial calcium overload, necrotic apoptosis signal pathways will be activated through the CaMKII-mPTP or XO-ROS-mPTP pathway in the reperfused heart.…”