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Circulating dipeptidyl peptidase IV activity correlates with cardiac dysfunction in human and experimental heart

Leonardo dos Santos1, Thiago A Salles, Daniel F Arruda-Junior

  • 1Heart Institute.

Circulation. Heart Failure
|July 30, 2013
PubMed

Insights

Elevated dipeptidyl peptidase IV (DPPIV) activity is linked to worse heart failure outcomes. Inhibiting DPPIV with sitagliptin improved cardiac function and reduced disease progression in experimental models.

Area of Science:

  • Cardiovascular Research
  • Enzymology
  • Pharmacology

Background:

  • Dipeptidyl peptidase IV (DPPIV) inactivates cardioprotective peptides.
  • DPPIV activity's role in heart failure (HF) and its therapeutic potential are unclear.

Purpose of the Study:

  • To investigate the correlation between DPPIV activity and adverse outcomes in HF.
  • To explore the therapeutic efficacy of DPPIV inhibition in HF.

Main Methods:

  • Measured DPPIV activity in 190 HF patients and 42 controls.
  • Induced HF in rats via LV ablation and treated with sitagliptin.
  • Assessed hemodynamic, cardiac remodeling, and apoptosis markers.

Main Results:

  • HF patients showed ~130% higher DPPIV activity than controls.
  • DPPIV activity correlated inversely with ejection fraction and positively with LV end-diastolic pressure and lung congestion.
  • Sitagliptin treatment attenuated cardiac dysfunction, remodeling, apoptosis, and pulmonary congestion in rats.

Conclusions:

  • Circulating DPPIV activity is associated with poorer cardiovascular outcomes in human and experimental HF.
  • Long-term DPPIV inhibition mitigates HF development and progression.
Abstract

Keywords:
dipeptidyl peptidase IV inhibitorsglucagon-like peptide 1ventricular remodelingwater-electrolyte balance

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