Developing a panel of biomarkers and miRNA in patients with myocardial infarction for early intervention strategies of heart failure in West Virginian population

PLoS One. 2018 Oct 24;13(10):e0205329. doi: 10.1371/journal.pone.0205329. eCollection 2018.

Abstract

Background: Myocardial infarction is the most common cause of heart failure. MI has been intricately linked to ventricular remodeling, subsequently leading to the reduction in the cardiac ejection fraction causing HF. The cumulative line of evidence suggests an important role of several biomarkers in modulating the cardiac vasculature, further contributing towards the progression of post-MI complications. Studies have demonstrated, yet not fully established, that an important biomarker, IL-10, has a causal relationship with MI and associated cardiac dysfunction.

Hypothesis: This study aims to establish the role of IL-10 as a prognostic marker for the cardiovascular outcomes and to develop a panel of biomarkers and circulating miRNAs that could potentially result in the early detection of HF resulting from MI, allowing for early intervention strategies.

Methods and results: Blood was withdrawn and echocardiography assessment was performed on a total of 43 patients that were enrolled, within 24 hours of the incidence of MI. Patients were divided in three main groups, based on the ejection fraction measurement from echocardiography: control (n = 14), MI with normal EF (MI+NEF, n = 13) and MI with low EF (MI+LEF, n = 16). Our results showed that TGFβ-1, TNF-α, IL-6 and MMP-9 were upregulated significantly in MI+NEF group and more so in MI+LEF group, as compared to control group (p<0.01). The circulating levels of miR-34a, miR-208b and miR-126 were positively correlated and showed elevated levels in the MI+NEF group, even higher in MI+LEF group, while levels of miR-24 and miR-29a were reduced in MI+NEF, and much lower in MI+LEF, as compared to the control group (p<0.01). Our results also demonstrated a direct correlation of IL-10 with the ejection fraction in patients with MI: IL-10 was elevated in MI+NEF group, however, the levels were significantly low in MI+LEF group suggesting an important role of IL-10 in predicting heart failure. Importantly, our study confirmed the correlation of IL-10 with EF by our follow-up echocardiography assessment that was performed 2 months after the incidence of MI.

Conclusion: Our results support the clinical application of these serum biomarkers to develop a panel for appropriate prognosis and management of adverse cardiac remodeling and development of heart failure post-myocardial infarction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood*
  • Echocardiography
  • Female
  • Gene Expression Regulation / genetics
  • Heart Failure / blood*
  • Heart Failure / diagnostic imaging
  • Heart Failure / epidemiology
  • Heart Failure / pathology
  • Humans
  • Interleukin-10 / blood*
  • Interleukin-10 / genetics
  • Male
  • Matrix Metalloproteinase 9 / blood
  • MicroRNAs / blood
  • Middle Aged
  • Myocardial Infarction / blood*
  • Myocardial Infarction / diagnostic imaging
  • Myocardial Infarction / genetics
  • Myocardial Infarction / pathology
  • Prognosis
  • Stroke Volume / genetics
  • Transforming Growth Factor beta / blood
  • Tumor Necrosis Factor-alpha / blood
  • Ventricular Function, Left / genetics
  • West Virginia / epidemiology

Substances

  • Biomarkers
  • IL10 protein, human
  • MicroRNAs
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • MMP9 protein, human
  • Matrix Metalloproteinase 9