Type II diabetes is recognized as a major risk factor for death due to cardiovascular complications such as coronary heart disease (CHD), but the complex interplay between these two diseases remains poorly understood. Suppression of oxidative stress, apoptosis, and inflammation of endothelial cells is a valuable treatment strategy to prevent or halt the progression of CHD. In the present study, we used real-time polymerase chain reaction (PCR), Western blot analysis, and enzyme linked immunosorbent assay (ELISA) to investigate the effects of saxagliptin on hypoxia-inducible factors. Our findings demonstrate that saxagliptin can significantly improve cell viability in H9c2 cells as well as reduce hypoxia-induced oxidative damage and loss of mitochondrial membrane potential. Saxagliptin reduced hypoxia-induced NADPH oxidase 4 (NOX 4). We also show that saxagliptin can reduce the expression of matrix metallopeptidase-2 (MMP-2) and matrix metallopeptidase-9 (MMP-9), two important degradative enzymes. Saxagliptin also suppressed hypoxia-induced expression of high mobility group box-1 protein (HMGB1), a key inflammatory cytokine. Finally, we show that saxagliptin can exert atheroprotective effects by reducing the expression of myeloid differential protein-88 (MyD88) and increasing the expression of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Thus, saxagliptin shows promise as a treatment against diabetes-associated CHD.
Keywords: DPP-4; Inflammation; Ischemic heart disease; MyD88; Saxagliptin.
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