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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

The contributions of dipeptidyl peptidase IV to inflammation in heart failure

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Autor(es):
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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]
Número total de Autores: 13
Afiliação do(s) autor(es):
[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
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY; v. 310, n. 11, p. H1760-H1772, JUN 1 2016.
Citações Web of Science: 11
Resumo

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)

Processo FAPESP: 11/07402-1 - Impacto da inibição da enzima dipeptidil peptidase IV sobre as alterações cardíacas e renais de ratos submetidos à injúria do miocárdio: avaliação dos efeitos preventivos e terapêuticos
Beneficiário:Thiago de Almeida Salles
Linha de fomento: Bolsas no Brasil - Doutorado Direto
Processo FAPESP: 13/10619-8 - Dipeptidil peptidase IV como um potencial alvo para a terapia da insuficiência cardíaca
Beneficiário:Adriana Castello Costa Girardi
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 09/54225-8 - Fisiopatologia da insuficiência cardíaca congestiva
Beneficiário:Paulo Jose Ferreira Tucci
Linha de fomento: Auxílio à Pesquisa - Temático