title: Inhibition of dipeptidyl peptidase-IV enzyme activity protects against myocardial ischemia-reperfusion injury in rats.
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).
  
  
  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 (DPP4(D)) rats (n = 16) were equally divided into DPP4(D)-SC and DPP4(D)-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 DPP4(D)-IR groups than in WT-SC and DPP4(D)-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 DPP4(D)-IR than those in other groups (all p <0.001).
  
  
  CONCLUSIONS
  Abrogation of DPP4 activity protects against myocardial IR injury and preserved heart function.
authors.forename: Sarah
authors.initials: S
authors.lastname: Chua
authors.forename: Fan-Yen
authors.initials: FY
authors.lastname: Lee
authors.forename: Tzu-Hsien
authors.initials: TH
authors.lastname: Tsai
authors.forename: Jiunn-Jye
authors.initials: JJ
authors.lastname: Sheu
authors.forename: Steve
authors.initials: S
authors.lastname: Leu
authors.forename: Cheuk-Kwan
authors.initials: CK
authors.lastname: Sun
authors.forename: Yung-Lung
authors.initials: YL
authors.lastname: Chen
authors.forename: Hsueh-Wen
authors.initials: HW
authors.lastname: Chang
authors.forename: Han-Tan
authors.initials: HT
authors.lastname: Chai
authors.forename: Chu-Feng
authors.initials: CF
authors.lastname: Liu
authors.forename: Hung-I
authors.initials: HI
authors.lastname: Lu
authors.forename: Hon-Kan
authors.initials: HK
authors.lastname: Yip
mesh_terms: D000818:Animals; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D018819:Dipeptidyl Peptidase 4