IGF-1 affects the development of myocarditis in LDL-R knockout mice by inhibiting peritoneal infiltration of macrophages

H.-D. Li, B. Chen, F. Yang

Department of Cardiovascular Medicine, Linyi Central Hospital, Linyi, Shandong, China. dusu3860210@yeah.net

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• Cardiology

OBJECTIVE: Infiltration of the inflammatory cells, such as macrophages and myocardial necrosis, are involved in myocarditis. Insulin-like growth factor (IGF-1) exerts a variety of biological effects. However, the role of IGF-1 in myocarditis remains unclear.
PATIENTS AND METHODS: LDL-R knockout mice were randomly divided into the control group, myocarditis group, and IGF-1 siRNA group. Real Time-Polymerase Chain Reaction (PCR) and Western blot were used to measure IGF-1 expression in myocardial tissue. The myocardial tissue changes were analyzed by HE staining. The total cholesterol (TC) and low-density lipoprotein cholesterol (LDL) in each group were detected. Flow cytometry was used to analyze the number of macrophages. The secretion of TNF-α and INF-γ and macrophage migration inhibitory factor (MIF) were detected by enzyme-linked immunosorbent assay (ELISA).
RESULTS: Compared with the control group, IGF-1 expression, TC, and LDL in myocarditis group was significantly increased, along with decreased heart rate (HR), left ventricular end-systolic diameter (LVEDs), left ventricular end-diastolic diameter (LVEDd), and left ventricular mass index (LVMI). In addition, inflammatory cell infiltration, fibrosis, and macrophages number in the peritoneum were increased. Moreover, the secretion of TNF-α, INF-γ, and MIF was also significantly increased (p<0.05). However, IGF-1 siRNA treatment inhibited IGF-1 expression and reversed the changes in the myocarditis group with statistically significant differences compared with the myocarditis group (p<0.05).
CONCLUSIONS: IGF-1 expression is increased in myocarditis. The downregulation of IGF-1 expression inhibits macrophages infiltration, reduces the expression of MIF and inflammatory factors, and improves myocarditis injury.

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