Circulating p53-Responsive microRNAs are Predictive Indicators of Heart Failure after Acute Myocardial Infarction
Rationale: Despite a recent decline of in-hospital mortality due to acute myocardial infarction (AMI), the incidence of ischemic heart failure (HF) in post-AMI patients is increasing. Although various microRNAs have been proposed as diagnostic indicators for AMI, no microRNAs have been established as predictors of ischemic HF that develop after AMI.
Objective: We attempted to identify circulating microRNAs that can serve as reliable predictors of ischemic HF in post-AMI patients.
Methods and Results: Using sera collected a median of 18 days after AMI onset, we screened microRNAs in 21 patients who developed HF within one year after AMI, and in 65 matched controls free from subsequent cardiovascular events after discharge. Among the 377 examined microRNAs, the serum level of only miR-192 was significantly up-regulated in AMI patients who developed ischemic HF. As miR-192 is reported to be p53-responsive, the serum levels of two other p53-responsive microRNAs, miR-194 and miR-34a, were also investigated. Interestingly, both microRNAs were coordinately increased with miR-192, particularly in exosomes, suggesting that these microRNAs function as circulating regulators of HF development via the p53 pathway. Furthermore, miR-194 and miR-34a expression levels were significantly correlated with left ventricular end-diastolic dimension one year after AMI.
Conclusions: In the sera of post-AMI patients who developed HF within one year of AMI onset, the levels of three p53-responsive microRNAs were elevated by the early convalescent stage of AMI. Further investigations are warranted to confirm the usefulness of these circulating microRNAs for predicting the risk of developing ischemic HF after AMI.
- Received February 18, 2013.
- Revision received June 4, 2013.
- Accepted June 6, 2013.