Aim: Matrix-degrading metalloproteases (MMPs) play an essential role in the atherogenic process, from the initial lesion to plaque rupture. A growing body of evidence show that inhibition of MMP activity or rebalancing the MMP/TIMP (tissue inhibitor of MMP) equilibrium has a potential therapeutic strategy for atherosclerosis. We studied the in vitro effects of newly designed peptides on MMP activity in endothelial cells and macrophages. Methods: Eight peptides were designed in silico and synthesized using the solid phase synthesis and characterized by circular dichroism and Dynamic Light Scattering. The mouse macrophage cell line J774A.1 and the human endothelial cell line EA.hy926 were treated with the peptides (10 µM and 10 µM) for 24 hours. Then, conditioned medium was collected and MMP-2, and MMP-9 activity was determined by gelatin gel zymography. Results: Analysis of the zymograms showed that upon 10 µM treatment in endothelial cells, three out of eight peptides reduced the activity of proMMP-9 and proMMP-2 by more than 60 and 40 percent, respectively. Whereas, upon treatment at 100 µM the proMMP-9 levels were less or not reduced. These could be consequent to aggregation of the peptide at a concentration higher than 50 µM. In macrophages, two of these peptides reduced the activity of proMMP-2 by more than 40 percent, but had no effect on proMMP-9 activity. The peptides, did not show any effects on MMP mRNA levels. Conclusions: These data show that these peptides show a promising inhibitory effect on MMP-9 and MMP-2 activity in endothelial cells and macrophages.
Novel MMP-inhibiting peptides for stabilizing atherosclerotic plaques / A. Abdali, H. Macut, S. Pellegrino, C. de Dominicis, M. Zanda, M.L. Gelmi, S. Bellosta. ((Intervento presentato al 85. convegno European Atherosclerosis Society (EAS) Congress : April, 23-26 tenutosi a Prague nel 2017.
|Titolo:||Novel MMP-inhibiting peptides for stabilizing atherosclerotic plaques|
ABDALI, ANAHITA (Primo)
MACUT, HELENA (Secondo)
GELMI, MARIA LUISA (Penultimo)
BELLOSTA, STEFANO (Ultimo)
|Data di pubblicazione:||24-apr-2017|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Citazione:||Novel MMP-inhibiting peptides for stabilizing atherosclerotic plaques / A. Abdali, H. Macut, S. Pellegrino, C. de Dominicis, M. Zanda, M.L. Gelmi, S. Bellosta. ((Intervento presentato al 85. convegno European Atherosclerosis Society (EAS) Congress : April, 23-26 tenutosi a Prague nel 2017.|
|Appare nelle tipologie:||14 - Intervento a convegno non pubblicato|