Potential Role of Dipeptidyl Peptidase IV in the Pathophysiology of Heart Failure

Author(s)

Salles, Thiago A. ^[1] ; dos Santos, Leonardo ^[2] ; Barauna, Valerio G. ^[2] ; Girardi, Adriana C. C. ^[1]

Affiliation

^[1] Univ Sao Paulo, Heart Inst InCor, Lab Genet & Mol Cardiol, Sch Med, BR-05403000 Sao Paulo, SP - Brazil

^[2] Univ Fed Espirito Santo, Dept Physiol Sci, BR-29043900 Vitoria, ES - Brazil

• Document type: Review article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 16, n. 2, p. 4226-4249, FEB 2015.
• Web of Science Citations: 11

Abstract

Dipeptidyl peptidase IV (DPPIV) is a widely expressed multifunctional serine peptidase that exists as a membrane-anchored cell surface protein or in a soluble form in the plasma and other body fluids. Numerous substrates are cleaved at the penultimate amino acid by DPPIV, including glucagon-like peptide-1 (GLP-1), brain natriuretic peptide (BNP) and stromal cell-derived factor-1 (SDF-alpha), all of which play important roles in the cardiovascular system. In this regard, recent reports have documented that circulating DPPIV activity correlates with poorer cardiovascular outcomes in human and experimental heart failure (HF). Moreover, emerging evidence indicates that DPPIV inhibitors exert cardioprotective and renoprotective actions in a variety of experimental models of cardiac dysfunction. On the other hand, conflicting results have been found when translating these promising findings from preclinical animal models to clinical therapy. In this review, we discuss how DPPIV might be involved in the cardio-renal axis in HF. In addition, the potential role for DPPIV inhibitors in ameliorating heart disease is revised, focusing on the effects of the main DPPIV substrates on cardiac remodeling and renal handling of salt and water. (AU)

• 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