title: The contributions of dipeptidyl peptidase IV to inflammation in heart failure.
abstract: Circulating dipeptidyl peptidase IV (DPPIV) activity correlates with cardiac dysfunction in humans and experimental heart failure (HF) models. Similarly, inflammatory markers are associated with poorer outcomes in HF patients. However, the contributions of DPPIV to inflammation in HF remain elusive. Therefore, this study aimed to investigate whether the cardioprotective effects of DPPIV inhibition after myocardial injury are accompanied by reduced cardiac inflammation, whether circulating DPPIV activity correlates with the levels of systemic inflammatory markers in HF patients, and whether leukocytes and/or splenocytes may be one of the sources of circulating DPPIV in HF. Experimental HF was induced in male Wistar rats by left ventricular myocardial injury after radiofrequency catheter ablation. The rats were divided into three groups: sham, HF, and HF + DPPIV inhibitor (sitagliptin). Six weeks after surgery, cardiac function, perfusion and inflammatory status were evaluated. Sitagliptin treatment improved cardiac function and perfusion, reduced macrophage infiltration, and diminished the levels of inflammatory biomarkers including TNF-α, IL-1β, and CCL2. In HF patients, serum DPPIV activity correlated with CCL2, suggesting that leukocytes may be the source of circulating DPPIV in HF. Unexpectedly, DPPIV release was higher in splenocytes from HF rats and similar in HF circulating mononuclear cells compared with those from sham, suggesting an organ-specific modulation of DPPIV in HF. Collectively, our data provide new evidence that the cardioprotective effects of DPPIV inhibition in HF may be due to suppression of inflammatory cytokines. Moreover, they suggest that a vicious circle between DPPIV and inflammation may contribute to HF development and progression.
authors.affiliation: Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil;
authors.forename: Thiago
authors.initials: T
authors.lastname: de Almeida Salles
authors.affiliation: Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil;
authors.forename: Camila
authors.initials: C
authors.lastname: Zogbi
authors.affiliation: Department of Clinical Medicine,University of São Paulo Medical School, São Paulo, Brazil;
authors.forename: Thais Martins
authors.initials: TM
authors.lastname: de Lima
authors.affiliation: Laboratory of Nuclear Medicine (LIM 43), University of São Paulo Medical School, São Paulo, Brazil;
authors.forename: Camila
authors.initials: C
authors.lastname: de Godoi Carneiro
authors.affiliation: Laboratory of Nuclear Medicine (LIM 43), University of São Paulo Medical School, São Paulo, Brazil;
authors.forename: Alexandre Teles
authors.initials: AT
authors.lastname: Garcez
authors.affiliation: Department of Clinical Medicine,University of São Paulo Medical School, São Paulo, Brazil;
authors.forename: Hermes Vieira
authors.initials: HV
authors.lastname: Barbeiro
authors.affiliation: Department of Physiology, Federal University of São Paulo, São Paulo, Brazil; and.
authors.forename: Ednei Luiz
authors.initials: EL
authors.lastname: Antonio
authors.affiliation: Department of Physiological Sciences, Federal University of Espírito Santo, Vitoria, Espírito Santo, Brazil.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Dos Santos
authors.affiliation: Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil;
authors.forename: Alexandre
authors.initials: A
authors.lastname: da Costa Pereira
authors.affiliation: Department of Physiology, Federal University of São Paulo, São Paulo, Brazil; and.
authors.forename: Paulo José Ferreira
authors.initials: PJ
authors.lastname: Tucci
authors.affiliation: Laboratory of Nuclear Medicine (LIM 43), University of São Paulo Medical School, São Paulo, Brazil;
authors.forename: Daniele
authors.initials: D
authors.lastname: de Paula Faria
authors.affiliation: Department of Clinical Medicine,University of São Paulo Medical School, São Paulo, Brazil;
authors.forename: Francisco Garcia
authors.initials: FG
authors.lastname: Soriano
authors.affiliation: Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil; adriana.girardi@incor.usp.br.
authors.forename: Adriana Castello Costa
authors.initials: AC
authors.lastname: Girardi
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D007249:Inflammation / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D053583:Interleukin-1beta / Q000097:blood; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D000068900:Sitagliptin Phosphate / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; D018932:Chemokine CCL2; D054873:Dipeptidyl-Peptidase IV Inhibitors; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D000068900:Sitagliptin Phosphate
keywords: cardiac dysfunction; glucagon-like peptide-1; proinflammatory cytokines; sitagliptin; spleen