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- Title
The complex P2 X<sub>7</sub> receptor/inflammasome in perivascular fat tissue of heavy smokers.
- Authors
Rossi, Chiara; Santini, Eleonora; Chiarugi, Massimo; Salvati, Antonio; Comassi, Mario; Vitolo, Edoardo; Madec, Stephanie; Solini, Anna
- 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 P2 X7 receptor ( P2 X7 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 P2 X7 R-inflammasome in this picture. Subjects and Methods TNFα, IL-6, RBP4, MCP-1, as well as P2 X7 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 P2 X7 R and inflammasome components; via P2 X7 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 P2 X7 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. Conclusion Smoking contributes to the pro-inflammatory status of the PVAT by enhancing expression and activity of the P2 X7 R-inflammasome complex; the effect on adipocytokines more related to insulin resistance and metabolic abnormalities appears trivial.
- Subjects
PURINERGIC receptors; HEALTH of cigarette smokers; CARDIOVASCULAR diseases risk factors; HEALTH; SMOKING; ADIPOSE tissues; ATHEROSCLEROSIS; DISEASE progression; INFLAMMATION
- Publication
European Journal of Clinical Investigation, 2014, Vol 44, Issue 3, p295
- ISSN
0014-2972
- Publication type
Academic Journal
- DOI
10.1111/eci.12232