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Inhibition of dipeptidyl peptidase-IV enzyme activity protects against myocardial ischemia-reperfusion injury in rats.
- Source :
-
Journal of Translational Medicine . 2014, Vol. 12 Issue 1, p607-636. 30p. - Publication Year :
- 2014
-
Abstract
- 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), WTIR, 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 (H&E), 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 14795876
- Volume :
- 12
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of Translational Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 100375703
- Full Text :
- https://doi.org/10.1186/s12967-014-0357-0