Circulating p53-Responsive MicroRNAs Are Predictive Indicators of Heart Failure After Acute Myocardial Infarction

Abstract

Rationale: Despite a recent decline of in-hospital mortality attributable 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 develops 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 experienced development of HF within 1 year after AMI and in 65 matched controls without subsequent cardiovascular events after discharge. Among the 377 examined microRNAs, the serum level of only miR-192 was significantly upregulated in AMI patients with development of ischemic HF. Because miR-192 is reported to be p53-responsive, the serum levels of 2 other p53-responsive microRNAs, miR-194 and miR-34a, also were 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 1 year after AMI. Conclusions: In the sera of post-AMI patients who experienced development of de-novo HF within 1 year of AMI onset, the levels of 3 p53-responsive microRNAs had been 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 development of ischemic HF after AMI.