Liraglutide improves myocardial fibrosis after myocardial infarction through inhibition of CTGF by activating cAMP in mice

OBJECTIVE: To study the role and mechanism of liraglutide in myocardial fibrosis after myocardial infarction (MI).

MATERIALS AND METHODS: A total of 72 C57/BL male mice were randomly divided into sham operation group (Sham group), myocardial infarction group (MI group), and liraglutide intervention group (Lira group). The left anterior descending coronary artery (LAD) of the mice in MI group and Lira group was ligated to establish the MI model. One week after the operation, the mice in Lira group were intraperitoneally injected with 100 μg/kg of liraglutide once a day for 4 weeks. The mice in Sham group and MI group were injected with the equal volume of normal saline. At the 5th week after the operation, the cardiac morphologic indexes and cardiac function indexes were measured by echocardiography. After an ultrasound, the heart specimens of the mice were immediately harvested by thoracotomy, and histomorphological hematoxylin-eosin (HE) staining, collagen fiber Masson staining, and immunohistochemical staining were performed. The infarction zone and the non-infarction zone were isolated from another heart specimen; the cyclic adenosine monophosphate (cAMP) and hydroxyproline content were determined; and the expression levels of transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF) were detected by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Western blotting.

RESULTS: Liraglutide improved the cardiac function of mice after myocardial infarction. Liraglutide improved the myocardial fibrosis in mice after myocardial infarction. Liraglutide increased cAMP in myocardial cells of mice after myocardial infarction. Liraglutide did not change the TGF-β1 expressions while reduced the CTGF expressions in infarct and non-infarct area of mice after myocardial infarction.

CONCLUSIONS: Liraglutide, through increasing the level of cAMP, could decrease the deposition of collagen fibers in myocardial tissues of mice after MI, reduce the degree of infiltration of collagen fibers in the infarction zone into the myocardium in the non-infarction zone and inhibit the adverse ventricular remodeling in the non-infarction zone, thus improving the cardiac function after MI.

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