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STAT3 在类风湿关节炎女性皮下脂肪组织中的高表达与心血管风险相关。

High Expression of STAT3 in Subcutaneous Adipose Tissue Associates with Cardiovascular Risk in Women with Rheumatoid Arthritis.

机构信息

Department of Rheumatology and Inflammation Research, Institution of Medicine, Sahlgrenska Academy at University of Gothenburg, 413 46 Gothenburg, Sweden.

Rheumatology Clinic, Sahlgrenska University Hospital, 413 45 Gothenburg, Sweden.

出版信息

Int J Mol Sci. 2017 Nov 13;18(11):2410. doi: 10.3390/ijms18112410.

Abstract

Despite the predominance of female patients and uncommon obesity, rheumatoid arthritis (RA) is tightly connected to increased cardiovascular morbidity. The aim of this study was to investigate transcriptional activity in the subcutaneous white adipose tissue (WAT) with respect to this disproportionate cardiovascular risk (CVR) in RA. CVR was estimated in 182 female patients, using the modified Systematic Coronary Risk Evaluation scale, and identified 93 patients with increased CVR. The overall transcriptional activity in WAT was significantly higher in patients with CVR and was presented by higher serum levels of WAT products leptin, resistin and IL-6 (all, < 0.001). CVR was associated with high WAT-specific transcription of the signal transducer and activator of transcription 3 () and the nuclear factor NF-kappa-B p65 subunit (), and with high transcription of serine-threonine kinase B () in leukocytes. These findings suggest Interleukin 6 (IL-6) and leptin take part in WAT-specific activation of . The binary logistic regression analysis confirmed an independent association of CVR with IL-6 in serum, and with in WAT. The study shows an association of CVR with transcriptional activity in WAT in female RA patients. It also emphasizes the importance of STAT3 regulatory circuits for WAT-related CVR in RA.

摘要

尽管女性患者居多且肥胖并不常见,但类风湿关节炎(RA)与心血管发病率增加密切相关。本研究旨在探讨 RA 患者皮下白色脂肪组织(WAT)中与不成比例的心血管风险(CVR)相关的转录活性。通过改良的系统性冠状动脉风险评估量表评估 182 名女性患者的 CVR,发现 93 名患者的 CVR 增加。CVR 患者的 WAT 总体转录活性明显较高,且血清 WAT 产物瘦素、抵抗素和白细胞介素 6(均<0.001)水平升高。CVR 与 WAT 中信号转导和转录激活因子 3(STAT3)和核因子κB p65 亚基(NF-κB p65)的高特异性转录以及白细胞中丝氨酸-苏氨酸激酶 B(AKT)的高转录相关。这些发现表明白细胞介素 6(IL-6)和瘦素参与了 WAT 中 STAT3 的特异性激活。二元逻辑回归分析证实了 CVR 与血清中 IL-6 以及 WAT 中 之间存在独立关联。该研究表明 CVR 与女性 RA 患者 WAT 中的转录活性相关,并强调了 STAT3 调节回路对 RA 中与 WAT 相关的 CVR 的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/47af/5713378/614e8665cad6/ijms-18-02410-g001.jpg

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