title: Cross-talk between the dipeptidyl peptidase-4 and stromal cell-derived factor-1 in stem cell homing and myocardial repair: Potential impact of dipeptidyl peptidase-4 inhibitors.
abstract: Dipeptidyl peptidase-4 (DPP-4), glycyl-prolyl-naphthylamidase, is a serine protease that catalyzes the hydrolysis of various proline-containing polypeptides. It is involved in the inactivation of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), having in this way a profound influence on glucose metabolism. During organ damage, stromal and endothelial cells produce a chemokine known as stromal cell-derived factor-1 (SDF-1), a powerful chemoattractant of stem/progenitor cells. SDF-1 binds to a specific α-chemokine receptor (CXCR4) and can be degraded by proteases, including matrix DPP-4/CD26, presented in the circulation, or activated in injured tissues. DPP-4 inhibition has received considerable attention because of its significant therapeutic benefits in the regulation of insulin secretion and tissue insulin sensitivity, the regulation of tumor growth and metastasis, angiogenesis, tissue repair, especially after myocardial infarction, and regulation of endocrine function. Inhibition of circulating proteases appears to maintain the optimal endogenous SDF-1 concentration and may enhance homing of endothelial progenitor cells. In the present article, we present an overview of some basic facts about the role of DPP-4 in glucose homeostasis, the mechanism of its inhibition, and a brief summary of available DPP-4 inhibitors. Furthermore, since protection against the overactivity of proteases is important for restorating cardiac function and repair after myocardial damage, necrosis and apoptosis, we propose that administration of a DPP-4 inhibitor may also be beneficial following myocardial infarction by the prevention of cleavage of stem cell chemoattractant cytokine SDF-1.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, SI-1000, Slovenia. Electronic address: marko.anderluh@ffa.uni-lj.si.
authors.forename: Marko
authors.initials: M
authors.lastname: Anderluh
authors.affiliation: Institute of Biochemistry, Faculty of Medicine, University of Nis, Bulevar Dr Zorana Djindjica 81, 18000 Nis, Serbia.
authors.forename: Gordana
authors.initials: G
authors.lastname: Kocic
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Nis, Bulevar Dr Zorana Djindjica 81, 18000 Nis, Serbia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Tomovic
authors.affiliation: Clinic for Endocrinology, Faculty of Medicine, University of Nis, Bulevar Dr Zorana Djindjica 48, 18000 Nis, Serbia.
authors.forename: Radivoj
authors.initials: R
authors.lastname: Kocic
authors.affiliation: Institute for Cardiovascular Rehabilitation, Faculty of Medicine, University of Nis, 18205 Niska Banja, Serbia.
authors.forename: Marina
authors.initials: M
authors.lastname: Deljanin-Ilic
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Nis, Bulevar Dr Zorana Djindjica 81, 18000 Nis, Serbia; Department of Chemistry, Faculty of Medicine, University of Nis, Bulevar Dr Zorana Djindjica 81, 18000 Nis, Serbia.
authors.forename: Andrija
authors.initials: A
authors.lastname: Smelcerovic
mesh_terms: D000818:Animals; D054377:Chemokine CXCL12 / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4 / Q000187:drug effects / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D042783:Endothelial Cells / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010447:Peptide Hydrolases / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism
chemical_list: D054377:Chemokine CXCL12; D054873:Dipeptidyl-Peptidase IV Inhibitors; D010447:Peptide Hydrolases; D018819:Dipeptidyl Peptidase 4; D005947:Glucose
keywords: Alogliptin (PubChem CID: 11450633); DPP-4 inhibitors; Dipeptidyl peptidase-4; Linagliptin (PubChem CID: 10096344); Myocardial repair; Saxagliptin (PubChem CID: 11243969); Sitagliptin (PubChem CID: 4369359); Stromal cell-derived factor-1; Vildagliptin (PubChem CID: 24848920)