Circulating microRNAs and the Occurrence of Acute Myocardial Infarction in Chinese Populations
Background—Circulating microRNAs (miRNAs) are emerging as novel disease biomarkers. We aimed to explore the association between circulating miRNAs and the occurrence of acute myocardial infarction (AMI) in Chinese populations.
Methods and Results—In the discovery stage, the plasma of 20 AMI patients and 20 controls were pooled respectively and profiled by massively parallel sequencing. Seventy-seven miRNAs showed differential expression. Selected miRNAs were validated in 178 AMI patients and 198 controls using quantitative reverse transcriptase polymerase chain reaction assays, and further replicated in 150 AMI patients and 150 controls. Results suggest that miR-320b and miR-125b levels were significantly lower in AMI patients than controls in both validation populations (p<0.0001). Lower levels of miR-320b and miR-125b were associated with increased occurrence of AMI (adjusted odds ratio [OR] 4.71, 95% confidence interval [CI] 2.96 to 7.48; OR 4.27, 95% CI 2.84 to 6.41, respectively). Addition of the two miRNAs to traditional risk factors led to a significant improvement in the area under the curve from 0.822 (95% CI, 0.787-0.856) to 0.871 (95% CI, 0.842-0.900), with a net reclassification improvement of 20.45% (p<0.0001) and an integrated discrimination improvement of 0.16 (p<0.0001) for AMI patients. A functional study showed that miR-320b and miR-125b could regulate the expression profiles of genes enriched in several signal transduction pathways critical for CHD in human vascular endothelial cells.
Conclusions—The plasma levels of miR-320b and miR-125b were significantly lower in AMI patients compared with controls, and these miRNAs may be involved in the pathogenesis of coronary heart disease.
- Received August 6, 2013.
- Revision received February 18, 2014.
- Accepted February 27, 2014.