DPP-4 inhibition has beneficial effects on the heart after myocardial infarction

Autor: Yoshio Kobayashi, Akihiko Kubota, Issei Komuro, Hiroyuki Takano, Tomoko Yamada-Inagawa, Hiroyuki Tadokoro, Hiroshi Hasegawa, Haixiu Wang, Yuka Kobara, Masanori Hirose
Rok vydání: 2016
Předmět:
Male
STAT3 Transcription Factor
0301 basic medicine
Cardiac function curve
Receptors
CXCR4
medicine.medical_specialty
Cardiotonic Agents
animal structures
Dipeptidyl Peptidase 4
Myocardial Infarction
Apoptosis
030204 cardiovascular system & hematology
Pharmacology
Ventricular Function
Left
Mice
03 medical and health sciences
0302 clinical medicine
Internal medicine
medicine
Animals
Myocytes
Cardiac
Myocardial infarction
STAT3
Molecular Biology
Dipeptidyl peptidase-4
Heart Failure
Mice
Knockout
Dipeptidyl-Peptidase IV Inhibitors
biology
business.industry
Myocardium
Endothelial Cells
medicine.disease
Chemokine CXCL12
Mice
Inbred C57BL
Endothelial stem cell
Disease Models
Animal
030104 developmental biology
Animals
Newborn
Gene Expression Regulation
Heart failure
biology.protein
Cardiology
Female
Cardiology and Cardiovascular Medicine
business
Signal Transduction
Zdroj: Journal of Molecular and Cellular Cardiology. 91:72-80
ISSN: 0022-2828
DOI: 10.1016/j.yjmcc.2015.12.026
Popis: 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 5 days 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-1α (SDF-1α) 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-1α/CXCR4-mediated STAT3 signaling pathway.
Databáze: OpenAIRE
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