Downregulation of interferon-induced protein with tetratricopeptide repeats 3 relieves the inflammatory response and myocardial fibrosis of mice with myocardial infarction and improves their cardiac function

• Published in: Experimental Animals Vol. 70; no. 4; pp. 522 - 531
• Main Authors: Sun, Jianhua, Zhang, Qi, Liu, Xiaokun, Shang, Xiaoming
• Format: Journal Article
• Language: English
• Published: Tokyo Japanese Association for Laboratory Animal Science 01.01.2021; Japan Science and Technology Agency
• Subjects: Animal tissues; Cardiac function; Cardiovascular diseases; Collagen; Coronary artery; Cytokines; Extracellular signal-regulated kinase; Fibrosis; Gene expression; Heart attacks; IL-1β; Inflammation; Inflammatory response; Interferon; interferon-induced protein with tetratricopeptide repeats 3 (IFIT3); Interleukin 6; Interleukins; Kinases; Macrophages; MAP kinase; mitogen-activated protein kinase (MAPK) pathway; Morbidity; Myocardial infarction; Original; Phosphorylation; Protein kinase; Proteins; RNA-mediated interference; Serum levels; Tumor necrosis factor-α
• ISSN: 1341-1357; 1881-7122
• DOI: 10.1538/expanim.21-0060

Myocardial infarction (MI) is a common cardiovascular disease with high morbidity and mortality. In this study, we explored the role of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) in MI. MI was induced by ligation of the left anterior descending coronary artery. Lentivirus-mediated RNA interference of IFIT3 expression was performed by tail vein injection 72 h before MI modeling. Cardiac injury indexes and inflammatory response were examined 3 days after MI. Cardiac function indexes, infarct size, and cardiac fibrosis were assessed 4 weeks after MI. IFIT3 expression was upregulated in myocardial tissues at both 3 days and 4 weeks after MI. Knockdown of IFIT3 significantly relieved the myocardial injury, as evidenced by the decrease in serum levels of cTnI and CK-MB. In addition, IFIT3 knockdown significantly reduced the number of CD68+ macrophages and the levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α, indicating that the inflammatory response was relieved. Moreover, IFIT3 silencing also significantly improved cardiac function and reduced infarct size, myocardial fibrosis, and collagen content in mice with MI. Mechanically, the present study showed that the activation of the mitogen-activated protein kinase (MAPK) pathway was observed in myocardial tissues of MI mice, which was blocked by IFIT3 knockdown, as indicated by the decreased phosphorylation of JNK, p-38, and ERK. Collectively, our results revealed the role of IFIT3 in the inflammatory response and myocardial fibrosis after MI, indicating that IFIT3 might be a potential target for MI treatment.