title: Resveratrol counteracts systemic and local inflammation involved in early abdominal aortic aneurysm development.
abstract: BACKGROUND
  Monocyte activation, macrophage infiltration, vascular oxidative stress and matrix proteolysis are inflammatory key steps contributing to abdominal aortic aneurysm (AAA) development. A phenotypical and functional heterogeneity is recognizable in monocytes by the differential expression of surface molecules: CD62L- subset corresponds to activated monocytes, while CD143/ACE surface expression increases during their differentiation into macrophages. In this work, Resveratrol, which is an antioxidant polyphenol with vasoprotective properties, has been evaluated for its potential to limit aneurysm development and monocyte-dependent inflammatory response in a model of elastase-induced AAA.
  
  
  METHODS
  Male Sprague-Dawley rats received Resveratrol (10 mg/kg/die) (Rsv group, n=15) or vehicle (ethanol) alone (Et-OH group, n=15) continuously from 7 d before until 14 d after the AAA induction with elastase; five littermates were used as untreated control group (Ctr group, n=5). At the end of treatment, CD143 and CD62L monocyte expression was analyzed by flow cytometry, serum antioxidant capacity was evaluated using the TRAP method and circulating TNFα, and MMP-9 were measured with ELISA and gel zymography, respectively. Aortas were subjected to histology and immunohistochemistry for morphological analysis, macrophage infiltration, and MMP-9, TNFα, and VEGF expression.
  
  
  RESULTS
  Resveratrol counteracted the CD62L-monocyte subset expansion, CD143 monocyte expression, and circulating levels of MMP-9 activity and TNFα associated to AAA induction. Similarly, treatment with Resveratrol significantly attenuated AAA expansion, vessel wall macrophage infiltration and MMP-9, VEGF, and TNFα expression, compared with AAA from Et-OH group.
  
  
  CONCLUSIONS
  Resveratrol limited the monocyte-dependent inflammatory response, macrophage differentiation and aortic lumen enlargement in elastase-induced AAA. These data suggest that Resveratrol might be tested in selected patients with small AAA to modulate the early systemic and local inflammatory response associated to AAA progression.
authors.affiliation: Experimental and Clinical Vascular Biology Lab, Vascular and Endovascular Surgery Unit, San Martino Hospital and Department of Internal Medicine, Research Center of Cardiovascular Biology, University of Genoa, Genoa, Italy. danielapalmieri@yahoo.com
authors.forename: Daniela
authors.initials: D
authors.lastname: Palmieri
authors.forename: Bianca
authors.initials: B
authors.lastname: Pane
authors.forename: Chiara
authors.initials: C
authors.lastname: Barisione
authors.forename: Giovanni
authors.initials: G
authors.lastname: Spinella
authors.forename: Silvano
authors.initials: S
authors.lastname: Garibaldi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Ghigliotti
authors.forename: Claudio
authors.initials: C
authors.lastname: Brunelli
authors.forename: Ezio
authors.initials: E
authors.lastname: Fulcheri
authors.forename: Domenico
authors.initials: D
authors.lastname: Palombo
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D017544:Aortic Aneurysm, Abdominal / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D019041:L-Selectin / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010196:Pancreatic Elastase / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014657:Vasculitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D019041:L-Selectin; D007703:Peptidyl-Dipeptidase A; D010196:Pancreatic Elastase; D020780:Matrix Metalloproteinase 9; D000077185:Resveratrol