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

Abstract

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 hours 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 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.

Integrative bioinformatic analysis identified IFIT3 as a novel regulatory factor in psoriasis

“…38 There is also study revealed that knockdown of IFIT3 relieved the inflammatory response and myocardial fibrosis after myocardial infarction. 39 However, the role of IFIT3 in other autoimmune diseases such as psoriasis remains unknown. Therefore, the previously screened IFN-related genes OAS1, USP18, and IFIT3 are significantly overexpressed in psoriasis and have not been previously studied, suggesting that OAS1, USP18, and IFIT3 play important roles in the pathogenesis of psoriasis.…”

“…The knockdown of IFIT3 could significantly suppress the release of inflammatory cytokines in hepatic ischemia‐reperfusion injury via the inhibition of STAT1 and STAT2 phosphorylation 38 . There is also study revealed that knockdown of IFIT3 relieved the inflammatory response and myocardial fibrosis after myocardial infarction 39 . However, the role of IFIT3 in other autoimmune diseases such as psoriasis remains unknown.…”

Identification of novel prognostic targets in coronary artery disease and related complications using bioinformatics and next generation sequencing data analysis

“…IFITM3 [49] expression is related to the patients with hypercholesterolemia and its progression. Previous studies have shown that IFIT3 [50] might influence the prognosis in myocardial infarction. IFIT1 [51] might be involved in the pathogenesis of atherosclerosis.…”

Screening key genes and signaling pathways in COVID-19 infection and its associated complications by integrated bioinformatics analysis

“…CXCL10 might play a role in progression of diabetes mellitus [68]. CXCL10 [69], ISG15 [70], SIGLEC1 [71], CXCL9 [72], IFIT3 [73], KLF15 [74] and SPRR3 [75] have a potential role in the diagnosis and treatment of cardiovascular diseases. CXCL10 [76], SIGLEC1 [77] and IL1R2 [78] have been suggested to be associated with neurological diseases.…”