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The complex P 2 X 7 receptor/inflammasome in perivascular fat tissue of heavy smokers
Author(s) -
Rossi Chiara,
Santini Eleonora,
Chiarugi Massimo,
Salvati Antonio,
Comassi Mario,
Vitolo Edoardo,
Madec Stephanie,
Solini Anna
Publication year - 2014
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/eci.12232
Subject(s) - inflammasome , adipose tissue , adipokine , insulin resistance , medicine , endocrinology , receptor , inflammation , tumor necrosis factor alpha , insulin
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 P 2 X 7 receptor ( P 2 X 7 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 P 2 X 7 R ‐inflammasome in this picture. Subjects and Methods TNF α, IL ‐6, RBP 4, MCP ‐1, as well as P 2 X 7 R and inflammasome components NLRP 3, ASC , caspase‐1 and IL ‐1β and IL ‐18 expression was determined in adipocytes isolated by PVAT of healthy smokers ( S mok) and nonsmokers ( N o‐ S mok) subjects. Plasma and culture medium levels of these cytokines were also determined. Results Perivascular adipose tissue of Smok had a higher expression of P 2 X 7 R and inflammasome components; via P 2 X 7 R activation, it released more IL ‐1β and IL ‐18, whose serum levels were also higher in S mok than in N o‐ S mok. Linear correlations of NLRP 3 with P 2 X 7 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 TNF α, RBP 4, IL ‐6; this was coupled with similar plasma levels of TNF α and RBP 4 in the two groups. Conclusion Smoking contributes to the pro‐inflammatory status of the PVAT by enhancing expression and activity of the P 2 X 7 R ‐inflammasome complex; the effect on adipocytokines more related to insulin resistance and metabolic abnormalities appears trivial.