MiR-223-3p affects myocardial inflammation and apoptosis following myocardial infarction via targeting FBXW7

Abstract

Background: Myocardial infarction (MI) is one of the main causes of disability and death in the world, leading to myocarditis and cardiomyocyte apoptosis. Studies have shown that microRNA (miRNA) is involved in myocarditis and apoptosis. The main purpose of this study was to explore the regulatory mechanism of miR-223-3p on myocarditis and apoptosis after MI. Methods: We cultured H9c2 cells and detected the expression of miR-223-3p in cells treated with different concentrations of H 2 O 2 . Sprague Dawley (SD) rats were fed with normal diet, constructed an MI model and detect the expression of miR-223-3p in heart tissue. Overexpression or inhibition of miR-223-3p was conducted in MI model cells in vitro, and the contents of the inflammatory factors tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) in cell supernatant were detected by enzymelinked immunosorbent assay (ELISA). Cell apoptosis was detected by flow cytometry. Luciferase activity assay was used to detect the targeting relationship between miR-223-3p and FBXW7, and the expression of FBXW7 in cells was also detected. Overexpression of miR-223-3p was performed in MI rats to detect the expression of inflammatory factors, FBXW7, and apoptosis in rat cardiac tissue. Results: The expression of miR-223-3p was down regulated in MI models established in vitro and in vivo. Overexpression of miR-223-3p can inhibit inflammatory response and apoptosis in H9c2 cells and cardiac tissues. It was revealed that miR-223-3p can inhibit the expression of FBXW7, reduce myocarditis and apoptosis after MI, and improve cardiac function. Conclusions: It is possible that miR-223-3p reduces myocarditis and apoptosis after MI and improves cardiac function by targeted inhibition of FBXW7 expression.

Platelet Internalization Mediates Ferroptosis in Myocardial Infarction

“…As a highly and specifically expressed miRNA in platelets, 28,46 miR-223-3p is involved in many pathological processes. 12,47 Besides ACSL3, Twist1, 48 TGFBR2, 48 FBXW7, 49 and SPI1 50 were also suppressed by miR-223-3p in cardiomyocytes. In our study, we did not examine the effect of platelet internalization on other functions of cardiomyocytes, but we do not rule out the possibility that increased miR-223-3p is also involved in arrhythmia 3 as well as cell necroptosis 51 and apoptosis.…”

lncRNA DLX6-AS1 Promotes Myocardial Ischemia-Reperfusion Injury through Mediating the miR-204-5p/FBXW7 Axis

“…FBXW7 is a F-box WD40 protein and serves as a substrate recognition subunit of the SCF (SKP1/CUL1/F-box protein) E3 ubiquitin ligase complex. In recent years, a lot of work has found that miR-223-3p targets FBXW7 to regulate myocardial inflammation and apoptosis after myocardial infarction [ 18 ]. Additionally, miR322 modulates the FBXW7/notch pathway to affect cardioprotection against IR injury [ 19 ].…”

“…A previous study has uncovered that FBXW7 expression was elevated in myocardial IR injury. Inhibition of FBXW7 significantly alleviated inflammatory response, cell apoptosis, and IR-induced myocardial injury in mice [ 18 , 19 ]. Thus, we speculated that DLX6-AS1 may alleviate myocardial IR injury by regulating miR-204-5p/FBXW7 axis.…”

Expression Patterns of MiR-125a and MiR-223 and Their Association with Diabetes Mellitus and Survival in Patients with Non-ST-Segment Elevation Acute Coronary Syndrome

“…Some authors have shown deleterious effects of increased miR-223, including enhancement of fibrosis [19] and stimulation of atherogenesis [20]. In contrast, other authors reported beneficial effects of elevated miR-223 expression, including protection against ischemia-reperfusion injury [21,22] and apoptosis, as well as myocarditis [23]. In a murine model, miR-223 ameliorated fibrosis, inflammation and apoptosis, and mediated angiogenesis [24].…”