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Anti‐inflammatory Effects of Dipeptidyl Peptidase IV (DPPIV) Inhibition in Heart Failure
Author(s) -
Salles Thiago,
Zogbi Camila,
Lima Thais,
Soriano Francisco,
Girardi Adriana
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.634.2
Subject(s) - sitagliptin , dipeptidyl peptidase 4 , medicine , inflammation , endocrinology , heart failure , dipeptidyl peptidase , proinflammatory cytokine , tumor necrosis factor alpha , pharmacology , type 2 diabetes , chemistry , diabetes mellitus , biochemistry , enzyme
DPPIV inhibitors are antidiabetic drugs that confer cardioprotection beyond glucose lowering. We have previously demonstrated that circulating DPPIV associates with poorer cardiovascular outcomes in human and experimental heart failure (HF) and that long‐term DPPIV inhibition mitigates the development and/or progression of HF in rats. Since inflammation plays a role on HF pathophysiology, we hypothesized that the cardioprotective effects of DPPIV may be accompanied by reduction of cardiac inflammation in experimental HF. HF was induced in Wistar rats by left ventricular (LV) radiofrequency ablation. Rats were divided into three groups: Sham, HF and HF+IDPPIV inhibitor (sitagliptin 80mg/kg/day). Six‐week treatment with sitagliptin significantly improved LV ejection fraction, LV end diastolic volume, cardiac perfusion and mitigated cardiac hypertrophy. Additionally, cardiac infiltrate of macrophages increased in HF rats and treatment with sitaglipitin remarkably attenuated it. Moreover, HF rats not only showed increased cardiac expression of DPPIV, but also presented increased levels of p38 phosphorylation, interleukin 1‐beta, tumor necrosis factor alpha and interleukin‐6 compared to sitagliptin‐treated animals. Corroborating with these results, interferon regulatory factor 5, a key factor for M1 macrophage polarization, was also increased in HF rats and DPPIV inhibition was capable of preventing it. Interestingly, some macrophages presented in the lesion expressed glucagon‐like peptide 1 receptor (GLP1R) and the GLP1R agonist exendin‐4 reduced secretion of pro‐inflammatory cytokines from macrophages in vitro. Collectively, our results demonstrate that DPPIV inhibition improves cardiac function and attenuates cardiac inflammation in HF.