The mechanism of miR-142-3p in coronary microembolization-induced myocardiac injury via regulating target gene IRAK-1

Qiang Su,Yuhan Sun,Zhenbai Qin,Binghui Kong,Xiangwei Lv,Lang Li,Ziliang Ye

doi:10.1038/s41419-019-1341-7

Abstract

Coronary microembolization (CME) is a common complication seen during primary percutaneous coronary intervention (pPCI). CME-induced myocardiac inflammation is the primary cause of myocardiac injury. Dysregulated miR-142-3p has been implicated in multiple cardiovascular diseases and is significantly downregulated in CME-induced myocardial injury. However, the role of miR-142-3p in CME-induced myocardial injury is unclear. This study herein built a porcine CME model by infusing microembolization spheres into the left anterior descending branch via a microcatheter, and detected the downregulation of miR-142-3p in the myocardial tissues of CME pigs. Echocardiography, hematoxylin basic fuchsin picric acid (HBFP) staining, and western blotting of NF-κB p65, TNF-α, IL-1β, and IL-6 showed that the pharmacological overexpression of miR-142-3p using agomiR has improved cardiac function and attenuated CME-induced myocardiac inflammatory response, while its inhibition using antagomiR demonstrated inverse effects. Moreover, in vitro experiments demonstrated IRAK-1 as a direct target gene of miR-142-3p. Luciferase reporter assays, quantitative real-time polymerase chain reaction and western blotting demonstrated its effects in controlling the inflammation of cardiomyocytes. It is noteworthy that miR-142-3p was found to be decreased in the plasma of STEMI patients undergoing pPCI with no-reflow, indicating a potential clinical relevance of miR-142-3p. The receiver–operator characteristic curve indicated that plasma miR-142-3p might be an independent predictor of no-reflow during pPCI in patients with STEMI. Therefore, overexpression of miR-142-3p acts as a novel therapy for CME-induced myocardial injury.

Highlights

Coronary microembolization (CME) is a common complication seen during the emergency treatment of acute myocardial infarction (AMI) by primary percutaneous coronary intervention, with an incidence rate of 15–20%1
Downregulation of miR-142-3p in the myocardiac tissue of CME pigs As described in the sections method, the porcine model of CME was established by infusing microembolization sphere into the left anterior descending branch via microcatheter
CME group showed a significant reduction in cardiac functions, as reflected by marked reductions of left ventricular ejection fraction (LVEF), fractional shortening (FS), and cardiac output (CO), while a rise in left ventricular end-diastolic diameter (LVEDd) (P < 0.05, Table 1 and Fig. 1a)

Summary

Introduction

Coronary microembolization (CME) is a common complication seen during the emergency treatment of acute myocardial infarction (AMI) by primary percutaneous coronary intervention (pPCI), with an incidence rate of 15–20%1. Previous studies have demonstrated that there were several inflammatory cells infiltrating from the peri-foci area of CME-induced myocardiac microinfarction, and is accompanied by excessive release of inflammatory factors. This in turn elicits local myocardial inflammatory response, and remains the key element that leads to post-CME myocaridal injury and progressive cardiac dysfunction[4,5]. Li et al further uncovered that extensive NF-κB activation results in the excessive release of inflammatory mediators (such as TNF-α and IL-1β), which played an important role in CME-induced progressive cardiac dysfunction and advanced heart failure. While CME-induced local myocardiac inflammatory response was prominently alleviated and the cardiac function was markedly improved after NF-κB activity was suppressed by a specific inhibitor

Methods

Results

Conclusion