Inhibition of dipeptidyl peptidase-IV enzyme activity protects against myocardial ischemia-reperfusion injury in rats

Journal of Translational Medicine

Hon-Kan Yip¹  Hung-I Lu³  Chu-Feng Liu⁵  Han-Tan Chai⁴  Hsueh-Wen Chang²  Yung-Lung Chen⁴  Cheuk-Kwan Sun⁵  Steve Leu⁶  Jiunn-Jye Sheu³  Tzu-Hsien Tsai⁴  Fan-Yen Lee³  Sarah Chua⁴ 

[1] Institute of Shock Wave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123, Dapi Road, Niaosung District, Kaohsiung City 83301, Taiwan, R.O.C;Department of Biological Sciences, National Sun Yat-Sen University, 70, Lienhai Road, Kaohsiung 80424, Taiwan, R.O.C;Department of Surgery, Division of Thoracic and Cardiovascular Surgery, Kaohsiung Chang Gung Memorial Hospital, 123, Dapi Road, Niaosung District, Kaohsiung City 83301, Taiwan, R.O.C;Department of Internal Medicine, Division of Cardiology, Kaohsiung Chang Gung Memorial Hospital, 123, Dapi Road, Niaosung District, Kaohsiung City 83301, Taiwan, R.O.C;Department of Emergency Medicine, E-DA Hospital, I-Shou University, 1, Yida Road, Jiaosu Village, Yanchao District, Kaohsiung City 82445, Taiwan, R.O.C;Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital, 123, Dapi Road, Niaosung District, Kaohsiung City 83301, Taiwan, R.O.C

关键词: Heart function;    Oxidative stress;    Inflammation;    Sitagliptin;    Dipeptidyl peptidase-IV (DPP4) enzyme;    Ischemia-reperfusion injury;   

Others  :  1146582
DOI  :  10.1186/s12967-014-0357-0

 received in 2014-07-26, accepted in 2014-12-04,  发布年份 2014

【 摘 要 】

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 (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).

Conclusion

Abrogation of DPP4 activity protects against myocardial IR injury and preserved heart function.

【 授权许可】

   
2014 Chua et al.; licensee BioMed Central.

【 图 表 】

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