The contributions of dipeptidyl peptidase IV to inflammation in heart failure

Author(s):Show less -

Salles, Thiago de Almeida ^[1] ; Zogbi, Camila ^[1] ; de Lima, Thais Martins ^[2] ; Carneiro, Camila de Godoi ^[3] ; Garcez, Alexandre Teles ^[3] ; Barbeiro, Hermes Vieira ^[2] ; Antonio, Ednei Luiz ^[4] ; dos Santos, Leonardo ^[5] ; Pereira, Alexandre da Costa ^[1] ; Ferreira Tucci, Paulo Jose ^[4] ; Faria, Daniele de Paula ^[3] ; Soriano, Francisco Garcia ^[2] ; Costa Girardi, Adriana Castello ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Med, Heart Inst InCor, Ave Dr Eneas de Carvalho Aguiar 44, 10 Andar, BR-05403900 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Sch Med, Dept Clin Med, Ave Dr Eneas de Carvalho Aguiar 44, 10 Andar, BR-05403900 Sao Paulo, SP - Brazil

^[3] Univ Sao Paulo, Sch Med, Lab Nucl Med LIM 43, Ave Dr Eneas de Carvalho Aguiar 44, 10 Andar, BR-05403900 Sao Paulo, SP - Brazil

^[4] Univ Fed Sao Paulo, Dept Physiol, Sao Paulo - Brazil

^[5] Univ Fed Espirito Santo, Dept Physiol Sci, Vitoria, ES - Brazil

• Document type: Journal article
• Source: AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY; v. 310, n. 11, p. H1760-H1772, JUN 1 2016.
• Web of Science Citations: 10

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-alpha, IL-1 beta, 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. (AU)

• FAPESP's process: 11/07402-1 - Impact of dipeptidyl peptidase IV inhibition on the cardiac and renal alterations in rats subjected to myocardial injury: evaluation of the preventive and therapeutic effects
• Grantee: Thiago de Almeida Salles
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 13/10619-8 - Dipeptidyl peptidase IV as a potential target for the therapy of heart failure
• Grantee: Adriana Castello Costa Girardi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 09/54225-8 - The pathophysiology of congestive heart failure: from the organ to tile molecules
• Grantee: Paulo Jose Ferreira Tucci
• Support Opportunities: Research Projects - Thematic Grants