Background: We investigated whether attenuating dipeptidyl peptidase-IV (DPP4) enzyme activity protected rat heart from ischemia-reperfusion (IR) injury (40-min left anterior descending coronary artery ligation followed by 72 h reperfusion). Methods and results: Adult male Fischer 344 rats (n = 24) were equally divided into sham-control (WT-SC), WT-IR, and WT-IR-Sita (oral sitagliptin 400 mg/kg/day for 3 days) groups, whereas adult male DPP4-deficiency (DPP4D) rats (n = 16) were equally divided into DPP4D-SC and DPP4D-IR groups. Animals were sacrificed at 72 h after reperfusion with collection of heart specimens. Infarct area (HandE), collagen deposition (Sirius-red stain), fibrotic area (Masson's trichrome), and fluorescent-ROS intensity (H2DCFDA-labeling myocardium) of left ventricle were significantly higher in WT-IR than those in other groups, significantly higher in WT-IR-Sita and DPP4D-IR groups than in WT-SC and DPP4D-SC groups (all p < 0.001), but there was no difference between the latter two groups. Protein expressions of oxidative stress (oxidized protein), reactive oxygen species (NOX-1, NOX-2), inflammation (TNF-α, NF-κB, MMP-9, VCAM-1), apoptosis (mitochondrial Bax, cleaved caspase-3 and PARP), myocardial damage markers (cytosolic cytochrome-C, γ-H2AX), and number of inflammatory cells (CD14+, CD68+, CD40+ cells) showed a pattern identical to that of histological changes among all groups (all p < 0.005), whereas markers of anti-apoptosis (Bcl-2) and mitochondrial integrity (mitochondrial cytochrome-C) as well as left ventricular ejection fraction showed an opposite pattern (all p < 0.001). Protein expressions of anti-oxidants (HO-1, NQO-1), angiogenesis factors (SDF-1α, CXCR4), and glycogen-like-peptide-1-receptor were significantly higher inWT-IR-Sita and DPP4D-IR than those in other groups (all p < 0.001). Conclusion: Abrogation of DPP4 activity protects against myocardial IR injury and preserved heart function.
CITATION STYLE
Chua, S., Lee, F. Y., Tsai, T. H., Sheu, J. J., Leu, S., Sun, C. K., … Yip, H. K. (2014). Inhibition of dipeptidyl peptidase-IV enzyme activity protects against myocardial ischemia-reperfusion injury in rats. Journal of Translational Medicine, 12(1). https://doi.org/10.1186/s12967-014-0357-0
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