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

• Published in: Cell death & disease 2019-01, Vol.10 (2), p.61-61, Article 61
• Main Authors: Su, Qiang, Lv, Xiangwei, Ye, Ziliang, Sun, Yuhan, Kong, Binghui, Qin, Zhenbai, Li, Lang
• Format: Article
• Language: English
• Subjects: 13/95; 42/41; 631/80/304; 692/699/75; 82; Animals; Antibodies; Apoptosis; Biochemistry; Biomedical and Life Sciences; Cardiac function; Cardiology; Cardiomyocytes; Cardiovascular diseases; Cell Biology; Cell Culture; Chromosome 3; Cytokines - metabolism; Disease; Echocardiography; Embolism - complications; Embolism - etiology; Female; Gene expression; HEK293 Cells; Hogs; Humans; IL-1β; Immunology; Inflammation; Interleukin 6; Interleukin-1 Receptor-Associated Kinases - genetics; Interleukin-1 Receptor-Associated Kinases - metabolism; IRAK protein; Ischemia; Life Sciences; Lipopolysaccharides - pharmacology; Male; MicroRNAs; MicroRNAs - blood; MicroRNAs - genetics; MicroRNAs - metabolism; Myocardial Infarction - surgery; Myocarditis - blood; Myocarditis - etiology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; NF-κB protein; Patients; Percutaneous Coronary Intervention - adverse effects; Picric acid; Polymerase chain reaction; Rats; Spheres; Swine; Transcription Factor RelA - metabolism; Transfection; Tumor necrosis factor-α; Western blotting
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-019-1341-7

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.