title: Red Grape Skin Polyphenols Blunt Matrix Metalloproteinase-2 and -9 Activity and Expression in Cell Models of Vascular Inflammation: Protective Role in Degenerative and Inflammatory Diseases.
abstract: Matrix metalloproteinases (MMPs) are endopeptidases responsible for the hydrolysis of various components of extracellular matrix. MMPs, namely gelatinases MMP-2 and MMP-9, contribute to the progression of chronic and degenerative diseases. Since gelatinases' activity and expression are regulated by oxidative stress, we sought to evaluate whether supplementation with polyphenol-rich red grape skin extracts modulated the matrix-degrading capacity in cell models of vascular inflammation. Human endothelial and monocytic cells were incubated with increasing concentrations (0.5-25 μg/mL) of Negroamaro and Primitivo red grape skin polyphenolic extracts (NSPE and PSPE, respectively) or their specific components (0.5-25 μmol/L), before stimulation with inflammatory challenge. NSPE and PSPE inhibited, in a concentration-dependent manner, endothelial invasion as well as the MMP-9 and MMP-2 release in stimulated endothelial cells, and MMP-9 production in inflamed monocytes, without affecting tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2. The matrix degrading inhibitory capacity was the same for both NSPE and PSPE, despite their different polyphenolic profiles. Among the main polyphenols of grape skin extracts, trans-resveratrol, trans-piceid, kaempferol and quercetin exhibited the most significant inhibitory effects on matrix-degrading enzyme activities. Our findings appreciate the grape skins as rich source of polyphenols able to prevent the dysregulation of vascular remodelling affecting degenerative and inflammatory diseases.
authors: National Research Council-Institute of Clinical Physiology (CNR-IFC), Laboratory of Nutrigenomic and Vascular Biology, Lecce 73100, Italy. nadia.calabriso@ifc.cnr.it.
authors: Nadia
authors: N
authors: Calabriso
authors: National Research Council-Institute of Clinical Physiology (CNR-IFC), Laboratory of Nutrigenomic and Vascular Biology, Lecce 73100, Italy. marika.massaro@ifc.cnr.it.
authors: Marika
authors: M
authors: Massaro
authors: National Research Council-Institute of Clinical Physiology (CNR-IFC), Laboratory of Nutrigenomic and Vascular Biology, Lecce 73100, Italy. egeria.scoditti@ifc.cnr.it.
authors: Egeria
authors: E
authors: Scoditti
authors: National Research Council-Institute of Clinical Physiology (CNR-IFC), Laboratory of Nutrigenomic and Vascular Biology, Lecce 73100, Italy. mariangela_pellegrino@yahoo.it.|Department of Biological and Environmental Science and Technologies (DISTEBA), University of Salento, Lecce 73100, Italy. mariangela_pellegrino@yahoo.it.
authors: Mariangela
authors: M
authors: Pellegrino
authors: National Research Council-Institute of Science of Food Production, Lecce 73100, Italy. ilariaingrosso1@virgilio.it.
authors: Ilaria
authors: I
authors: Ingrosso
authors: National Research Council-Institute of Science of Food Production, Lecce 73100, Italy. giovanna.giovinazzo@ispa.cnr.it.
authors: Giovanna
authors: G
authors: Giovinazzo
authors: National Research Council-Institute of Clinical Physiology (CNR-IFC), Laboratory of Nutrigenomic and Vascular Biology, Lecce 73100, Italy. maria.carluccio@ifc.cnr.it.
authors: Maria Annunziata
authors: MA
authors: Carluccio
mesh_terms: D005638:Fruit / Q000737:chemistry*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D008954:Models, Biological; D059808:Polyphenols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D066253:Vascular Remodeling / Q000187:drug effects; D014657:Vasculitis / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D027843:Vitis / Q000737:chemistry*
chemical_list: D059808:Polyphenols; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: antioxidants; endothelium; flavonols; gelatinases; gene expression; grape skin polyphenolic extracts; inflammation; monocytes; phenolic acids; stilbenes