Abstract | BACKGROUND: METHODS AND RESULTS: After surgical LAD- ligation (left anterior descending artery), Sitagliptin/ Vildagliptin was applied yielding sufficient blood levels verified by mass spectrometry and significantly reducing activity of dipeptidyl peptidase (DPP) IV. GCSF or saline was administered intraperitoneally for 6 days. We assessed stem cell mobilization and homing (flow cytometry), infarct size (histology), neovascularization and cellular proliferation (immunohistology), heart function (Millar tip catheterization) and survival (Kaplan-Meier-curves). Gliptins±GCSF administration increased mobilization and cardiac homing of bone-marrow derived stem cells by stabilization of cardiac SDF1 (stromal cell-derived factor). For Sitagliptin, it could be shown that resident cardiac stem cells were stimulated, neovascularization was enhanced and cardiac remodeling was reduced. These effects finally improved myocardial function and increased survival for both gliptins. Although gliptins as a mono therapy lead to remarkable effects in a dose dependent manner and were superior to G-CSF mono- therapy, dual application of GCSF and gliptins revealed the best results. Since both gliptins yielded comparable effects concerning stem cell homing, cardiac function and survival, we suggest a class-effect of DPP-IV-inhibitors. CONCLUSIONS: Thus, gliptins+GCSF and in high concentrations even as mono therapy have beneficial effects on cardiac regeneration after myocardial infarction beyond its anti-diabetic potential.
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Authors | Hans D Theiss, Lisa Gross, Markus Vallaster, Robert David, Stefan Brunner, Christoph Brenner, Petra Nathan, Gerald Assmann, Josef Mueller-Hoecker, Michael Vogeser, Gerhard Steinbeck, Wolfgang-M Franz |
Journal | International journal of cardiology
(Int J Cardiol)
Vol. 168
Issue 4
Pg. 3359-69
(Oct 09 2013)
ISSN: 1874-1754 [Electronic] Netherlands |
PMID | 23669105
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2013 Elsevier Ireland Ltd. All rights reserved. |
Chemical References |
- Hypoglycemic Agents
- Nitriles
- Pyrazines
- Pyrrolidines
- Triazoles
- Granulocyte Colony-Stimulating Factor
- Vildagliptin
- Adamantane
- Sitagliptin Phosphate
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Topics |
- Adamantane
(administration & dosage, analogs & derivatives)
- Animals
- Cell Survival
(drug effects, physiology)
- Drug Therapy, Combination
- Granulocyte Colony-Stimulating Factor
(administration & dosage)
- Heart
(drug effects, physiology)
- Hypoglycemic Agents
(administration & dosage)
- Male
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Myocardial Infarction
(drug therapy)
- Nitriles
(administration & dosage)
- Pyrazines
(administration & dosage)
- Pyrrolidines
(administration & dosage)
- Sitagliptin Phosphate
- Triazoles
(administration & dosage)
- Vildagliptin
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