title: Antidiabetic gliptins in combination with G-CSF enhances myocardial function and survival after acute myocardial infarction.
abstract: BACKGROUND
  Medical stimulation of endogenous progenitor cell circulation may serve as a new therapeutic tool for treatment of acute myocardial infarction. We analyzed the effects of antidiabetic gliptins plus GCSF (granulocyte colony stimulating factor) on myocardial regeneration after myocardial infarction in a mouse model.
  
  
  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.
authors.affiliation: Medical Department I, Klinikum Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Hans D
authors.initials: HD
authors.lastname: Theiss
authors.forename: Lisa
authors.initials: L
authors.lastname: Gross
authors.forename: Markus
authors.initials: M
authors.lastname: Vallaster
authors.forename: Robert
authors.initials: R
authors.lastname: David
authors.forename: Stefan
authors.initials: S
authors.lastname: Brunner
authors.forename: Christoph
authors.initials: C
authors.lastname: Brenner
authors.forename: Petra
authors.initials: P
authors.lastname: Nathan
authors.forename: Gerald
authors.initials: G
authors.lastname: Assmann
authors.forename: Josef
authors.initials: J
authors.lastname: Mueller-Hoecker
authors.forename: Michael
authors.initials: M
authors.lastname: Vogeser
authors.forename: Gerhard
authors.initials: G
authors.lastname: Steinbeck
authors.forename: Wolfgang-M
authors.initials: WM
authors.lastname: Franz
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004359:Drug Therapy, Combination; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000188:drug therapy*; D009570:Nitriles / Q000008:administration & dosage*; D011719:Pyrazines / Q000008:administration & dosage*; D011759:Pyrrolidines / Q000008:administration & dosage*; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000008:administration & dosage*; D000077597:Vildagliptin
chemical_list: D007004:Hypoglycemic Agents; D009570:Nitriles; D011719:Pyrazines; D011759:Pyrrolidines; D014230:Triazoles; D016179:Granulocyte Colony-Stimulating Factor; D000077597:Vildagliptin; D000218:Adamantane; D000068900:Sitagliptin Phosphate
keywords: Acute myocardial infarction; DPP-IV; G-CSF; Sitagliptin; Stem cell homing