title: Circulating dipeptidyl peptidase IV activity correlates with cardiac dysfunction in human and experimental heart failure.
abstract: BACKGROUND
  The present study addresses the hypothesis that the activity of dipeptidyl peptidase IV (DPPIV), an enzyme that inactivates peptides that possess cardioprotective actions, correlates with adverse outcomes in heart failure (HF). The therapeutic potential of DPPIV inhibition in preventing cardiac dysfunction is also investigated.
  
  
  RESULTS
  Measurements of DPPIV activity in blood samples obtained from 190 patients with HF and 42 controls demonstrated that patients with HF exhibited an increase of ≈130% in circulating DPPIV activity compared with healthy subjects. Furthermore, an inverse correlation was observed between serum DPPIV activity and left ventricular (LV) ejection fraction in patients with HF. Similarly, radiofrequency LV ablation-induced HF rats displayed higher DPPIV activity in the plasma (≈50%) and heart tissue (≈3.5-fold) compared with sham-operated rats. Moreover, positive correlations were observed between the plasma DPPIV activity and LV end-diastolic pressure and lung congestion. Two days after surgery, 1 group of LV ablation-induced HF rats was treated with the DPPIV inhibitor sitagliptin (40 mg/kg BID) for 6 weeks, whereas the remaining rats were administered water. Hemodynamic measurements demonstrated that radiofrequency LV-ablated rats treated with sitagliptin exhibited a significant attenuation of HF-related cardiac dysfunction, including LV end-diastolic pressure, systolic performance, and chamber stiffness. Sitagliptin treatment also attenuated cardiac remodeling and cardiomyocyte apoptosis and minimized pulmonary congestion.
  
  
  CONCLUSIONS
  Collectively, the results presented herein associate circulating DPPIV activity with poorer cardiovascular outcomes in human and experimental HF. Moreover, the results demonstrate that long-term DPPIV inhibition mitigates the development and progression of HF in rats.
authors.affiliation: Heart Institute.
authors.forename: Leonardo
authors.initials: L
authors.lastname: dos Santos
authors.forename: Thiago A
authors.initials: TA
authors.lastname: Salles
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Arruda-Junior
authors.forename: Luciene C G
authors.initials: LC
authors.lastname: Campos
authors.forename: Alexandre C
authors.initials: AC
authors.lastname: Pereira
authors.forename: Ana Luiza T
authors.initials: AL
authors.lastname: Barreto
authors.forename: Ednei L
authors.initials: EL
authors.lastname: Antonio
authors.forename: Alfredo J
authors.initials: AJ
authors.lastname: Mansur
authors.forename: Paulo J F
authors.initials: PJ
authors.lastname: Tucci
authors.forename: José E
authors.initials: JE
authors.lastname: Krieger
authors.forename: Adriana C C
authors.initials: AC
authors.lastname: Girardi
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D018819:Dipeptidyl Peptidase 4 / Q000097:blood*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011654:Pulmonary Edema / Q000201:enzymology / Q000517:prevention & control; D011719:Pyrazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000494:pharmacology; D015854:Up-Regulation; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D015415:Biomarkers; D054873:Dipeptidyl-Peptidase IV Inhibitors; D011719:Pyrazines; D014230:Triazoles; D020097:Natriuretic Peptide, Brain; D052216:Glucagon-Like Peptide 1; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D000068900:Sitagliptin Phosphate
keywords: dipeptidyl peptidase IV inhibitors; glucagon-like peptide 1; ventricular remodeling; water-electrolyte balance