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Circulating Dipeptidyl Peptidase IV Activity Correlates With Cardiac Dysfunction in Human and Experimental Heart Failure

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Autor(es):
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dos Santos, Leonardo [1, 2] ; Salles, Thiago A. [2] ; Arruda-Junior, Daniel F. [2] ; Campos, Luciene C. G. [2] ; Pereira, Alexandre C. [2] ; Barreto, Ana Luiza T. [2] ; Antonio, Ednei L. [3] ; Mansur, Alfredo J. [2] ; Tucci, Paulo J. F. [3] ; Krieger, Jose E. [2] ; Girardi, Adriana C. C. [2]
Número total de Autores: 11
Afiliação do(s) autor(es):
[1] Univ Fed Espirito Santo, Dept Physiol Sci, Vitoria - Brazil
[2] Univ Sao Paulo, Heart Inst InCor, Sch Med, BR-05403900 Sao Paulo - Brazil
[3] Univ Sao Paulo, Univ Fed Sao Paulo, Dept Physiol, BR-05403900 Sao Paulo - Brazil
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: Circulation-Heart Failure; v. 6, n. 5, p. 1029-1038, SEP 2013.
Citações Web of Science: 73
Resumo

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. Methods and 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 approximate to 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 (approximate to 50%) and heart tissue (approximate to 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. (AU)

Processo FAPESP: 07/52945-8 - Importância do peptídeo semelhante ao glucagon 1 (GLP-1) na manutenção do volume extracelular: abordagem funcional, farmacológica e molecular
Beneficiário:Adriana Castello Costa Girardi
Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores
Processo FAPESP: 09/54225-8 - Fisiopatologia da insuficiência cardíaca congestiva
Beneficiário:Paulo Jose Ferreira Tucci
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 12/10146-0 - Mecanismos moleculares da regulação da função tubular proximal na hipertensão arterial
Beneficiário:Adriana Castello Costa Girardi
Linha de fomento: Auxílio à Pesquisa - Regular