Assessment of dipeptidyl peptidase IV activity and expression in endothelial cells and lymphocytes of rats with heart failure: pathophysiological implications

• Grant number: 13/02742-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2013
• End date: April 30, 2014
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Adriana Castello Costa Girardi
• Grantee: Marina Silva Araújo
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

The enzyme dipeptidyl peptidase IV (DPPIV) is a serine protease that can be found anchored to the cell membrane in several tissues or insoluble form in plasma. Its function is to cleave peptide chains in which there is an alanine or proline as the second amino acid from the N-terminus. DPPIV substrates such as brain natriuretic peptide, glucagon-like peptide-1, and stromal-derived factor-1 alpha are of great importance in the cardiovascular system. Recent data from our laboratory have shown that rats with heart failure (HF) display an increase in the activity and abundance of DPPIV in plasma and cardiac endothelium. However, the stimulus that increases the circulating level and activity of DPPIV in HF remains to be determined. Moreover, there are very few studies in the literature regarding the soluble form of DPPIV. The origin of plasma DPPIV has been attributed to its proteolytic cleavage from the surface of peripheral lymphocytes, especially T-lymphocytes, through an as yet unidentified sheddase. Since the interaction endothelium-cardiomyocyte is essential for cardiac homeostasis, the increase of DPPIV activity and expression in endothelial cells, with subsequent cleavage of cardioprotective peptides, may lead to a number of pathological changes. Besides changes in cardiac tissue, increased peripheral vascular resistance has also been observed in HF, due at least partly to endothelial dysfunction. In light of the above, we propose to explore the role of DPPIV in the pathophysiology of heart failure. More specifically, the following hypotheses will be tested: (I) that the increasing levels of DPPIV in plasma of HF rats occurs due to decreased expression of this enzyme in lymphocytes, (II) that the activity and the expression of the enzyme DPPIV are increased in endothelial cells in HF rats and increased catalytic activity of DPPIV is correlated with endothelial dysfunction and with poor prognosis and HF, (III) the HF treatment decreases the expression and activity of endothelial and plasma DPPIV. (AU)