MicroRNA 3113-5p is a novel marker for early cardiac ischemia/reperfusion injury

Abstract

BackgroundIschemia/reperfusion (I/R) injury of heart is one of the major causes of acute cardiac injury, which may result in worsening or even loss of heart function. With novel microRNAs being evolutionarily discovered, numbers of them remained functionally unknown. We aimed to discover novel microRNAs with therapeutic or diagnostic potential in the setting of early cardiac I/R injury.MethodsCardiac electrical activity, biochemical detection and histopathology analysis were performed to reveal early changes of cardiac I/R injury. A microRNA array was performed to screen differential microRNAs in the mouse model of cardiac I/R injury. The differentially expressed microRNAs were validated in cardiac tissues and in serum samples.ResultsThe abnormality in electrocardiogram and increases in serum cTnI levels suggested the successful establishment of cardiac I/R injury in mice. A total of 1882 microRNAs were identified, of which 11 were significantly down-regulated and 41 were significantly up-regulated at 3 h post reperfusion. microRNA 223-3p and microRNA 3113-5p were among the mostly altered microRNAs and were validated to be up-regulated within the early hours of I/R injury in heart tissues. In the circulating system, cTnI, a sensitive marker of cardiac injury, or microRNA 223-3p only increased within the first 6 h post I/R injury. However, microRNA 3113-5p stably increased in the serum, keeping an increase of 2.5-fold throughout the 24 h. In the human serum samples, microRNA 3113-5p was detected to be significantly upregulated as soon as 3 h after I/R stimuli and kept significantly higher levels within the 48 h.ConclusionThis is the first study that reported the functional roles of microRNA 3113-5p in cardiovascular system. Our data suggested that cardiac microRNA 3113-5p might be a useful target for therapeutic purposes and circulating microRNA 3113-5p might serve as a stable marker for early diagnosis of cardiac I/R injury.

miR-3113-5p, miR-223-3p, miR-133a-3p, and miR-499a-5p are sensitive biomarkers to diagnose sudden cardiac death

“…We thus assessed whether four cardio-miRNAs (miR-3113-5p, miR-223-3p, miR-499a-5p, and miR-133a-3p) had any diagnostic values. The selection of these miRNAs was based on published literature [ 28 , 30 , 31 ] and our previous work [ 26 ] . Our aims were two-fold: one to assess whether these miRNAs could diagnose SCD, and the other one to assess whether specific miRNAs had higher efficacy as to discriminate the causes of SCD.…”

“…miR-223 was upregulated in a rat model of AMI and its overexpression promoted cardiac arrhythmias [ 23 ]; thus, miR-223 may be a new target in the treatment of ischemic arrhythmias. Our previous research showed that cardiac miR-3113-5p might be a useful target for therapeutic purposes and circulating miR-3113-5p might serve as a stable marker for early diagnosis of cardiac ischemia-reperfusion injury [ 26 ]. miR-499-5p is highly conserved and preferentially expressed in the myocardium [ 41 ]; circulating levels of miR-499-5p were significantly higher at admission in AMI patients that died within the following year as compared to those who survived the cardiovascular event [ 42 ].…”

“…miRNA-499 levels were found to be linearly proportional to myocardial damage, with close relationship with AMI [ 25 ]. Our previous work has identified miRNA-3113-5p as a novel cardio-miRNA that is significantly increased after cardiac ischemia-reperfusion (I/R) injury in cardiac and circulating levels and miRNA-3113-5p might serve as a stable marker for diagnosis of cardiac I/R injury [ 26 ]. All these miRNAs have been identified as originating from the heart or being heart-resided, making them possible candidates for the diagnostic biomarkers of cardiovascular diseases.…”

miR-3113-5p, miR-223-3p, miR-133a-3p, and miR-499a-5p are Sensitive Biomarkers to Diagnose Sudden Cardiac Death

“…miR-223 was upregulated in a rat model of AMI and its overexpression promoted cardiac arrhythmias [26]; thus, miR-223 may be a new target in the treatment of ischemic arrhythmias. Our previous research showed that cardiac miR-3113-5p might be a useful target for therapeutic purposes and circulating miR-3113-5p might serve as a stable marker for early diagnosis of cardiac ischemiareperfusion injury [33]. miR-499-5p is highly conserved and preferentially expressed in the myocardium [44], circulating levels of miR-499-5p were signi cantly higher at admission in AMI patients that died within the following year as compared to those that survived the cardiovascular event [45].…”

“…We thus assessed whether four cardio-miRNAs (miR-3113-5p, miR-223-3p, miR-499a-5p, and miR-133a-3p) had any diagnostic values. The selection of these miRNAs was based on published literature [30][31][32] and our previous work [33] . Our aims were two-fold: one to assess whether these miRNAs could diagnose SCD, and the other one to assess whether speci c miRNAs had higher e cacy as to discriminate the causes of SCD.…”