The complex P2X7 receptor/inflammasome in perivascular fat tissue of heavy smokers
The complex P2X7 receptor/inflammasome in perivascular fat tissue of heavy smokers
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DOI：
10.1111/eci.12232
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发表时间：
2014-03-01
影响因子：
5.5
通讯作者：
Solini, Anna
中科院分区：
文献类型：
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作者：
Rossi, Chiara;Santini, Eleonora;Solini, Anna
吸烟是公认的心血管危险因素。血管周围内脏脂肪组织（PVAT）是炎症分子的来源，因此有助于动脉粥样硬化的进展。P2 X（7）受体（P2 X（7）R）-炎性体复合物参与了这种情况，该复合物在决定IL-1和IL-18释放中至关重要。我们评估了吸烟是否可能影响PVAT炎症表型，并探讨了轴P2 X（7）R-炎性体在这张图片中的假定作用。在通过PVAT分离的健康吸烟者（Smok）和非吸烟者（No-Smok）受试者的脂肪细胞中测定胱天蛋白酶-1和IL-1和IL-18的表达。结果Smok大鼠血管周围脂肪组织中P2 X（7）R和炎性小体成分表达增高，通过P2 X（7）R的激活，释放出更多的IL-1和IL-18，Smok大鼠血清中IL-1和IL-18的水平也高于No-Smok大鼠。NLRP 3与P2 X（7）R和IL-18表达和释放呈线性相关。烟雾也有较高的PVAT表达的趋化因子MCP-1。然而，在PVAT中，与胰岛素抵抗密切相关的基因如TNF、RBP 4、IL-6的表达无明显差异，这与两组中相似的血浆TNF和RBP 4水平有关。结论吸烟通过增强P2 X（7）R-炎性体复合物的表达和活性而促进PVAT的促炎状态;对与胰岛素抵抗和代谢异常更相关的脂肪细胞因子的影响似乎微不足道。
ObjectiveSmoking is a recognized cardiovascular risk factor. Perivascular visceral adipose tissue (PVAT) is a source of inflammatory molecules, thus contributing to atherosclerosis progression. The P2X(7) receptor (P2X(7)R)-inflammasome complex, crucial in determining IL-1 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 P2X(7)R-inflammasome in this picture.Subjects and MethodsTNF, IL-6, RBP4, MCP-1, as well as P2X(7)R and inflammasome components NLRP3, ASC, caspase-1 and IL-1 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.ResultsPerivascular adipose tissue of Smok had a higher expression of P2X(7)R and inflammasome components; via P2X(7)R activation, it released more IL-1 and IL-18, whose serum levels were also higher in Smok than in No-Smok. Linear correlations of NLRP3 with P2X(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, RBP4, IL-6; this was coupled with similar plasma levels of TNF and RBP4 in the two groups.ConclusionSmoking contributes to the pro-inflammatory status of the PVAT by enhancing expression and activity of the P2X(7)R-inflammasome complex; the effect on adipocytokines more related to insulin resistance and metabolic abnormalities appears trivial.