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

Abstract

BackgroundSudden cardiac death (SCD) remains a great health threat and diagnostic challenge, especially those cases without positive autopsy findings. Molecular biomarkers have been urgently needed for the diagnosis of SCD displaying negative autopsy results. Due to their nature of stability, microRNAs (miRNAs) have emerged as promising diagnostic biomarkers for cardiovascular diseases. MethodsThis study investigated whether specific cardio-miRNAs (miR-3113-5p, miR-223-3p, miR-499a-5p, and miR-133a-3p) could serve as potential biomarkers for the diagnosis of SCD. Thirty-four SCD cases were selected, 18 categorized as acute myocardial infarction (AMI) without positive autopsy findings and 16 as atherosclerotic cardiovascular diseases (ASCVD) with gross myocardial scar. Carbon monoxide (CO) intoxication (n=14) and fatal injury death (n=14) that displayed no pathological changes of myocardium were selected as control group, respectively. Histological analyses were performed to reveal the pathological changes and real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression of those miRNAs. Resultsit showed that heart samples from the AMI group displayed no remarkable difference with regard to the expression of cleaved-caspase3, CD31, and CD68 and the extent of fibrotic tissue accumulation when compared with control samples. The four cardio-miRNAs were significantly up-regulated in the SCD samples as compared with control. When discriminating SCD from controls, ROC curve analysis revealed that the areas under the curve (AUC) of these 4 miRNAs were from 0.7839 to 0.9043 with sensitivity of 64.71-97.06% and specificity of 70-100%. Moreover, when discriminating the specific causes of SCD, the four miRNA expressions increased in the AMI heart as relative to ASCVD, and a combination of two miRNAs presented higher diagnostic value (AUC=0.7407-0.8667). ConclusionmiR-3113-5p, miR-223-3p, miR-499a-5p, and miR-133a-3p may serve as independent diagnostic biomarkers for SCD, and a combination of two of these miRNAs could further discriminate detailed causes of SCD.

Role of Global Longitude Strain related miRNAs as potential prognostic indicators in myocardial infarction

“…This indicats that miR-144-3p-mediated PTEN regulation may be a new therapeutic target for myocardial brosis after myocardial infarction. Yan et 31 found that miR-499a-5p was signi cantly upregulated in Sudden cardiac death samples compared with control samples, which may serve as an independent diagnostic biomarker for sudden cardiac death. A recent systematic review 28 demonstrated that miR-499a-5p and miR-1-3p are promising MI biomarkers because of their satisfactory diagnostic accuracy and short time window (within 4 hours of symptoms).…”