Food peptides reduce angiotensin II or interleukin 1β-induced cyclooxigenase-2 expression in vascular fibroblasts

Abstract

Resumen del póster presentado al 21st European Meeting on Hypertension and Cardiovascular Prevention celebrado en Milan (Italia) del 17 al 20 de junio de 2011.[Background/Aims]: Adventitial layer, mainly composed by fibroblasts (FB), plays a critical role in the regulation of the vascular structure and function and it is the principal source of superoxide anion that contributes to vascular remodeling and cell differentiation and proliferation. Moreover, this tissue hasan important expression of cyclooxygenase-2 (COX-2) induced by angiotensin II (Ang II) and proinflammatory cytokines like IL-1ß, which may contribute to the production of prostanoids in the inflammatory process related to cardiovascular pathologies as hypertension or atherosclerosis. Bioactive peptides are certain fragments within the sequence of food proteins that may show biological activity once released by enzymatic hydrolysis. In our previous research we demonstrated the antihypertensive properties of some of these peptides (Miguel et al. J Food Protect, 2004, 67:1914-20; Miguel et al. J Agric Food Chem 2006, 54:726-31; Miguel et al. J Agric Food Chem 2007, 55:10615-21). The aim of this study was to investigate the effect of antihypertensive peptides derived from food proteins on COX-2 expression in adventitial fibroblasts stimulated by Ang II or IL-1ß. [Methods]: Investigations were performed in isolated FB from aorta of Sprague-Dawley rats. The FB were incubated with different peptide sequences (RADHP, YAEERYPIL, IVF, IPP, VPP, ESIINF, YPI, RDILNQ, YRGGLEPINF; 100 μM), 1 hour before the incubation with Ang II (0.1 μM) or IL-1ß for 4 hours. COX-1 and COX-2 expression were determined by Western blot analysis. To evaluate if the peptides could affect to expression at the transcriptional level, we performed transitory co-transfection in FB with a reporter plasmid containing COX-2 promoter and a plasmid containing ß-galactosidase gene to quantify luciferase activity and to normalize with beta-galactosidase activity. [Results]: The treatment with Ang II or IL-1ß induced COX-2 expression on adventitial FB. However, COX-2 expression induced by Ang II was inhibited in the presence of the sequences VPP, RDILNQ and YRGGLEPINF. None of our peptides modify COX-1 expression. Transiently transfected cells incubated with Ang II or IL-1ß showed significant induction of luciferase activity compared with the control cells, however, transfected cells incubated with RDILNQ, YRGGLEPINF and VPP showed a significant and differential reduction of luciferase activity to almost basal levels according to stimuli. Conclusion: Our results suggest that the inhibitory properties in COX-2 expression induced by Ang II or IL-1ß observed in the sequences RDILNQ, YRGGLEPINF and VPP may be involucred in the capacity of regulated the arterial blood pressure.Peer Reviewe