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 SCD with negative autopsy (SCD-negative autopsy) findings and 16 as SCD with positive autopsy (SCD-positive autopsy) findings such as coronary atherosclerosis and 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 SCD-negative autopsy 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, receiver operating characteristic (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 heart from the SCD-negative autopsy group as relative to that from the SCD-positive autopsy group, 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.
Highlights
Sudden cardiac death (SCD) remains a great health threat and diagnostic challenge, especially those cases without positive autopsy findings
SCD-negative autopsy cases were not identified of any gross cardiovascular change as similar with control cases, while 56.2% (n = 9) of SCD-positive autopsy cases showed coronary stenosis (50–75% stenosis), calcification and myocardial fibrosis, and the remaining 43.8% (n = 7) showed coronary stenosis (> 75%), severe myocardial fibrosis and disorder (Table 2 and Fig. 1)
CD31 is involved in angiogenesis, leukocyte transmigration and integrin activation, and the changes of CD31-positive cells are commonly observed during cardiac remodeling [29]
Summary
Sudden 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. Irregular cardiac activities can restrict blood supply and lead to sudden cardiac death (SCD) [1], a condition that is defined as autopsy identification of a cardiac or vascular anomaly as the probable cause of death for seemingly healthy decedents [2]. Some SCD cases cannot be explained even after systemic autopsy and histological examination These cases have been postulated to die largely from AMI without grossly observable pathology [10]. It is an imperative to find sensitive biomarkers that could be used for detection of SCD, SCD with negative autopsy (SCD-negative autopsy) findings
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