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Research Article

DPP-4 inhibitor anagliptin protects against hypoxia-induced cytotoxicity in cardiac H9C2 cells

, , , , , , & show all
Pages 3823-3831 | Received 01 Jun 2019, Accepted 01 Aug 2019, Published online: 26 Sep 2019
 

Abstract

Cardiovascular complications are the leading cause of mortality and morbidity in type 2 diabetes patients. Diabetes greatly increases the risk of heart disease; therefore, the management of diabetes often involves the prevention of heart disease. DPP-4 inhibitors have been proven to be the effective therapeutic agents of glycaemic control. Recent studies have shown that certain types of DPP-4 inhibitors could also have cardiovascular benefits. In this study, we examined the protective role of the newly developed DPP-4 inhibitor anagliptin in cultured cardiac myocytic cell line H9C2 cells. Our data show that exposure of H9C2 cells to hypoxic conditions induced higher expression of DPP-4, indicating that DPP-4 is a hypoxia-inducible factor. The inhibition of DPP-4 by anagliptin ameliorates hypoxia-induced cytotoxicity and induction of the pro-inflammatory cytokines IL-6 and MCP-1. Anagliptin also suppresses hypoxia-induced oxidative stress as revealed by the detected levels of cellular ROS and reduced GSH. Moreover, anagliptin protects myocytes from hypoxia-associated reduced mitochondrial membrane potential. Mechanistically, we show that anagliptin promotes hypoxia-induced NFR2/HO1 induction but suppresses HMGB1 and MyD88 generation. Collectively, our data indicate that anagliptin-mediated DPP-4 inhibition is a protective mechanism in cardiomyocytes and imply that the DDP-4 inhibitor anagliptin plays dual roles by lowering glucose and protecting cardiomyocytes.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the grants from the Shanghai Science and Technology Commission [17411969400].