title: Effects of dipeptidyl peptidase-4 (DPP-4) inhibition on angiogenesis and hypoxic injury in type 2 diabetes.
abstract: OBJECTIVE
  We examined whether, in diabetic Ob/Ob mice, the dipeptidyl peptidase-4 (DPP-4) inhibitor (PKF275-055), an antihyperglycemic drug, that inhibits the biological inactivation of SDF-1 (stromal cell-derived factor-1), may increase endothelial progenitor cells (EPCs) mobilization and incorporation, which, in turn, may regenerate capillaries and reduce myocardial ischemia induced by strenuous exercise.
  
  
  METHODS
  Half of sixteen control and Ob/Ob mice and eight Ob/Ob mice treated with PKF275-055 for four weeks underwent a forced swim protocol. Oral glucose tolerance, circulating EPCs, capillary ultrastructure and density, hypoxic areas and SDF-1 localization in myocardium were measured.
  
  
  RESULTS
  Ob/Ob mice were glucose intolerant, had a significant low number of circulating EPCs and myocardial capillaries compared to lean controls. The DPP-4 inhibitor significantly improved their glucose tolerance, doubled the number of circulating EPCs, stimulated the formation of functional vessels and SDF-1 localization in the endothelium of myocardial capillaries and arterioles. Cardiac hypoxia after forced swim in Ob/Ob mice was significantly reduced when they were treated with the DPP-4 inhibitor.
  
  
  CONCLUSIONS
  DPP-4 inhibition may re-establish an adequate capillary network in the myocardium of diabetic Ob/Ob mice by the mobilization and SDF-1-mediated incorporation of EPCs and, consequently, reducing the susceptibility to myocardial ischemic injury provoked by strenuous exercise.
authors.affiliation: Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", 20156 Milan, Italy. Electronic address: fabio.fiordaliso@marionegri.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Fiordaliso
authors.affiliation: Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", 20156 Milan, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Maggioni
authors.affiliation: Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", 20156 Milan, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Balconi
authors.affiliation: Department of Environmental Health Sciences, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", 20156 Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Schiarea
authors.affiliation: Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", 20156 Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Corbelli
authors.affiliation: Department of Molecular Biochemistry and Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", 20156 Milan, Italy.
authors.forename: Ada
authors.initials: A
authors.lastname: De Luigi
authors.affiliation: Department of Biomedical Engineering, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", 24126 Bergamo, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Figliuzzi
authors.affiliation: Department of Neuroscience, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", 20156 Milan, Italy.
authors.forename: Xenia
authors.initials: X
authors.lastname: Antoniou
authors.affiliation: Department of Environmental Health Sciences, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", 20156 Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Chiabrando
authors.affiliation: Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", 20156 Milan, Italy.
authors.forename: Serge
authors.initials: S
authors.lastname: Masson
authors.affiliation: Department of Neuroscience, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", 20156 Milan, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Cervo
authors.affiliation: Department of Cardiovascular Research, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", 20156 Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Latini
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000188:drug therapy*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors
keywords: Angiogenesis; DPP-4 inhibitor; Diabetes; Myocardium; Strenuous exercise