title: The complex P2X7 receptor/inflammasome in perivascular fat tissue of heavy smokers.
abstract: OBJECTIVE
  Smoking is a recognized cardiovascular risk factor. Perivascular visceral adipose tissue (PVAT) is a source of inflammatory molecules, thus contributing to atherosclerosis progression. The P2X7 receptor (P2X7 R)-inflammasome complex, crucial in determining IL-1β and IL-18 release, participates in this scenario. We evaluated whether smoking might affect the PVAT inflammatory phenotype and explored the putative role of the axis P2X7 R-inflammasome in this picture.
  
  
  METHODS
  TNFα, IL-6, RBP4, MCP-1, as well as P2X7 R and inflammasome components NLRP3, ASC, caspase-1 and IL-1β and IL-18 expression was determined in adipocytes isolated by PVAT of healthy smokers (Smok) and nonsmokers (No-Smok) subjects. Plasma and culture medium levels of these cytokines were also determined.
  
  
  RESULTS
  Perivascular adipose tissue of Smok had a higher expression of P2X7 R and inflammasome components; via P2X7 R activation, it released more IL-1β and IL-18, whose serum levels were also higher in Smok than in No-Smok. Linear correlations of NLRP3 with P2X7 R and IL-18 expression and release emerged. Smok also had a higher PVAT expression of the chemotactic factor MCP-1. However, no difference was observed in the PVAT expression of genes more strictly related to insulin resistance, like TNFα, RBP4, IL-6; this was coupled with similar plasma levels of TNFα and RBP4 in the two groups.
  
  
  CONCLUSIONS
  Smoking contributes to the pro-inflammatory status of the PVAT by enhancing expression and activity of the P2X7 R-inflammasome complex; the effect on adipocytokines more related to insulin resistance and metabolic abnormalities appears trivial.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Rossi
authors.forename: Eleonora
authors.initials: E
authors.lastname: Santini
authors.forename: Massimo
authors.initials: M
authors.lastname: Chiarugi
authors.forename: Antonio
authors.initials: A
authors.lastname: Salvati
authors.forename: Mario
authors.initials: M
authors.lastname: Comassi
authors.forename: Edoardo
authors.initials: E
authors.lastname: Vitolo
authors.forename: Stephanie
authors.initials: S
authors.lastname: Madec
authors.forename: Anna
authors.initials: A
authors.lastname: Solini
mesh_terms: D017667:Adipocytes / Q000276:immunology / Q000378:metabolism*; D000328:Adult; D053468:CARD Signaling Adaptor Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D020170:Caspase 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D058847:Inflammasomes / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000166:cytology* / Q000276:immunology; D008297:Male; D008638:Mesenteric Arteries; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D058486:Receptors, Purinergic P2X7 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D054839:Retinol-Binding Proteins, Plasma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012720:Severity of Illness Index; D012907:Smoking / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D053468:CARD Signaling Adaptor Proteins; C111835:CCL2 protein, human; D002352:Carrier Proteins; D018932:Chemokine CCL2; D003598:Cytoskeletal Proteins; C508585:IL1B protein, human; C508600:IL6 protein, human; D058847:Inflammasomes; D020382:Interleukin-18; D053583:Interleukin-1beta; D015850:Interleukin-6; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C402202:PYCARD protein, human; C101326:RBP4 protein, human; D058486:Receptors, Purinergic P2X7; D054839:Retinol-Binding Proteins, Plasma; D014409:Tumor Necrosis Factor-alpha; D020170:Caspase 1
keywords: Inflammasome; P2X7 receptor; perivascular adipose tissue; smoking