title: Potential role of dipeptidyl peptidase IV in the pathophysiology of heart failure.
abstract: Dipeptidyl peptidase IV (DPPIV) is a widely expressed multifunctional serine peptidase that exists as a membrane-anchored cell surface protein or in a soluble form in the plasma and other body fluids. Numerous substrates are cleaved at the penultimate amino acid by DPPIV, including glucagon-like peptide-1 (GLP-1), brain natriuretic peptide (BNP) and stromal cell-derived factor-1 (SDF-α), all of which play important roles in the cardiovascular system. In this regard, recent reports have documented that circulating DPPIV activity correlates with poorer cardiovascular outcomes in human and experimental heart failure (HF). Moreover, emerging evidence indicates that DPPIV inhibitors exert cardioprotective and renoprotective actions in a variety of experimental models of cardiac dysfunction. On the other hand, conflicting results have been found when translating these promising findings from preclinical animal models to clinical therapy. In this review, we discuss how DPPIV might be involved in the cardio-renal axis in HF. In addition, the potential role for DPPIV inhibitors in ameliorating heart disease is revised, focusing on the effects of the main DPPIV substrates on cardiac remodeling and renal handling of salt and water.
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo 05403-000, SP, Brazil. sallesth@gmail.com.
authors.forename: Thiago A
authors.initials: TA
authors.lastname: Salles
authors.affiliation: Department of Physiological Sciences, Federal University of Espírito Santo, Vitoria 29043-900, ES, Brazil. leodossantos@hotmail.com.
authors.forename: Leonardo
authors.initials: L
authors.lastname: dos Santos
authors.affiliation: Department of Physiological Sciences, Federal University of Espírito Santo, Vitoria 29043-900, ES, Brazil. valerio.barauna@ufes.br.
authors.forename: Valério G
authors.initials: VG
authors.lastname: Barauna
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, São Paulo 05403-000, SP, Brazil. adriana.girardi@incor.usp.br.
authors.forename: Adriana C C
authors.initials: AC
authors.lastname: Girardi
mesh_terms: D000818:Animals; D054377:Chemokine CXCL12 / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use; D052216:Glucagon-Like Peptide 1 / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D020097:Natriuretic Peptide, Brain / Q000378:metabolism
chemical_list: D054377:Chemokine CXCL12; D054873:Dipeptidyl-Peptidase IV Inhibitors; D020097:Natriuretic Peptide, Brain; D052216:Glucagon-Like Peptide 1; D018819:Dipeptidyl Peptidase 4