Literature DB >> 24372548

The complex P2X7 receptor/inflammasome in perivascular fat tissue of heavy smokers.

Chiara Rossi1, Eleonora Santini, Massimo Chiarugi, Antonio Salvati, Mario Comassi, Edoardo Vitolo, Stephanie Madec, Anna Solini.   

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. SUBJECTS AND 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.
CONCLUSION: 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.
© 2013 Stichting European Society for Clinical Investigation Journal Foundation.

Entities:  

Keywords:  Inflammasome; P2X7 receptor; perivascular adipose tissue; smoking

Mesh:

Substances:

Year:  2014        PMID: 24372548     DOI: 10.1111/eci.12232

Source DB:  PubMed          Journal:  Eur J Clin Invest        ISSN: 0014-2972            Impact factor:   4.686


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