| First Author | Kubota A | Year | 2016 |
| Journal | J Mol Cell Cardiol | Volume | 91 |
| Pages | 72-80 | PubMed ID | 26739213 |
| Mgi Jnum | J:250830 | Mgi Id | MGI:6102054 |
| Doi | 10.1016/j.yjmcc.2015.12.026 | Citation | Kubota A, et al. (2016) DPP-4 inhibition has beneficial effects on the heart after myocardial infarction. J Mol Cell Cardiol 91:72-80 |
| abstractText | AIMS: Dipeptidyl peptidase-4 (DPP-4) inhibitors are reported to have protective effects on various cells but it is unclear how DPP-4 inhibitors have cardioprotective effects. Our aim was to study the mechanisms of cardioprotective effects by DPP-4 inhibition. METHODS AND RESULTS: C57BL/6 mice and DPP-4 knockout (DPP-4KO) mice were subjected to left coronary artery ligation to produce acute myocardial infarction (MI). C57BL/6 mice were then treated with vehicle or DPP-4 inhibitor. Left ventricular function, infarct size, the number of vessels, and myocardial ischemia were assessed at 5days after MI. The treatment with DPP-4 inhibitor significantly improved cardiac function and decreased the infarct size. DPP-4 inhibitor increased the ratio of endothelial cell numbers to a cardiomyocyte. The extent of myocardial ischemia and the number of TUNEL-positive cells in the border area were significantly decreased by DPP-4 inhibitor. Stromal cell-derived factor-1alpha (SDF-1alpha) level in myocardium was significantly increased by DPP-4 inhibitor. Those cardioprotective effects after MI were also recognized in DPP-4KO mice. DPP-4 protein was expressed on rat neonatal cardiomyocytes and DPP-4 inhibitor significantly reduced hypoxia-induced apoptosis in the cardiomyocytes. However, this effect was abolished by the pretreatment with a CXCR4 antagonist or a signal transducer and activator of transcription 3 (STAT3) inhibitor. The beneficial effects of DPP-4 inhibitor on heart failure after MI were abolished by cardiomyocyte-specific deletion of STAT3. CONCLUSIONS: DPP-4 inhibition may have direct protective effects on the post-MI heart by inducing an antiapoptotic effect and inhibiting a decrease in vessel number through the SDF-1alpha/CXCR4-mediated STAT3 signaling pathway. |
