Sitagliptin inhibits EndMT in vitro and improves cardiac function of diabetic rats through the SDF-1α/PKA pathway

Y. Wu, M. Xu, H. Bao, J.-H. Zhang

Department of Endocrine, Shanxian Central Hospital, Heze, Shandong, China. zhangguohuihehe@163.com

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• Pharmacology

OBJECTIVE: The aim of this paper was to study sitagliptin in improving the endothelial-mesenchymal transition (EndMT) of human aortic endothelial cells (HAECs) and cardiac function of rats with diabetes mellitus (DM) and its possible pathway.

MATERIALS AND METHODS: Sprague Dawley (SD) rats were divided into control group, DM group and sitagliptin group. The myocardial contraction and relaxation functions of rats in each group were observed via echocardiography. The changes in cardiac structure and fiber were observed via hematoxylin-eosin (HE) staining, Masson staining and Sirius red staining. The immunohistochemical assay was performed to observe the expressions of α-smooth muscle actin (α-SMA) and VE-cadherin in HAECs; the expression of reactive oxygen species (ROS) in HAECs was detected using the fluorescence probe. Moreover, the expressions of transforming growth factor-β1 (TGF-β1), phosphorylated-protein kinase A (p-PKA), PKA and extracellular signal-regulated kinase (ERK) were observed via Western blotting.

RESULTS: Sitagliptin could improve the myocardial contraction and relaxation functions in diabetic rats and EndMT and ROS production in HAECs. In the DM group, the expression of Glucagon-like peptide-1 (GLP-1) was decreased, while the expression of stromal-derived factor-1α (SDF-1α) was decreased and the expressions of downstream PKA/ERK pathway and TGF-β1 were increased. The above changes could be reversed by sitagliptin.

CONCLUSIONS: Sitagliptin can reverse the EndMT in HAECs as well as the cardiac function in diabetic rats through the SDF-1α/PKA pathway.

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