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

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, p < 0.001). CVR was associated with high WAT-specific transcription of the signal transducer and activator of transcription 3 (STAT3) and the nuclear factor NF-kappa-B p65 subunit (RELA), and with high transcription of serine-threonine kinase B (AKT1) in leukocytes. These findings suggest Interleukin 6 (IL-6) and leptin take part in WAT-specific activation of STAT3. The binary logistic regression analysis confirmed an independent association of CVR with IL-6 in serum, and with STAT3 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.

Retracted: Long non‐coding RNA XIST binding to let‐7c‐5p contributes to rheumatoid arthritis through its effects on proliferation and differentiation of osteoblasts via regulation of STAT3

“…Interestingly, the upregulation of STATs caused by pro‐inflammatory cytokines or growth factors is conductive to the pathogenesis of RA 42 . Besides, multiple lines of evidences have revealed that high expression of STAT3 contributes to the development of RA 43‐45 . More importantly, previously conducted study has suggested lncRNA XIST upregulates STAT3 to facilitate the development of retinoblastoma through binding with miR‐124 46 .…”

“…42 Besides, multiple lines of evidences have revealed that high expression of STAT3 contributes to the development of RA. [43][44][45] More importantly, previously conducted study has suggested lncRNA XIST upregulates STAT3 to facilitate the development of retinoblastoma through binding with miR-124. 46 All these findings provided strong support for our results that lncRNA XIST bound to let-7c-5p to upregulate STAT3 expression in RA.…”

Low serum IGF1 is associated with hypertension and predicts early cardiovascular events in women with rheumatoid arthritis

“…Complementary DNA was synthesized using High Capacity cDNA Reverse Transcription kit (Applied Biosystems, Foster City, CA). Amplification of the gene product was attained on a ViiA™7 Real-Time PCR (Applied Biosystems) using SYBR Green qPCR Mastermix (SA Biosciences, Qiagen) and primer pairs as reported [33, 40]. Gene expression levels were calculated by the ddCt method and presented as relative quantity to the average expression in the IGF1 hi group.…”

Low Soluble Receptor for Advanced Glycation End Products Precedes and Predicts Cardiometabolic Events in Women With Rheumatoid Arthritis

“…The measurement of adipokines and cytokines were determined using specific sandwich ELISA kits according to the instructions from the manufacturers (R&D Systems, Minneapolis, MN, USA) as previously described ( 28 ). The inflammatory parameters, blood lipids and RF/ACPA antibodies were measured at the accredited Laboratory of Clinical Chemistry at the Sahlgrenska University Hospital according to clinical routines.…”