Background Rheumatoid arthritis (RA) is an established risk factor for premature development of cardiovascular disease. Adipokines are signal molecules originating from adipose tissue and exhibit strong proinflammatory effects. We have previously shown that resistin utilizes IGF-1R (1) and TLR4 (2) pathway to induce inflammation in RA leukocytes and synovia.
Objectives In the present study we evaluated the role of adipokines and adipokine-related genes on the cardiovascular risk in female RA patients.
Methods The estimated cardiovascular risk was calculated in 187 female RA patients, using the modified Systematic Coronary Risk Evaluation (mSCORE). Serum levels of adipokines and IGF-1 and transcription of genes affected by Resistin and IGF-1 signalling in peripheral blood leukocytes and in subcutaneous fat tissue were analyzed in relation to mSCORE. To assess the predictive value of adipokines and gene transcription for the increased mSCORE, two independent binary logistic regression models were designed where high mSCORE or high resistin were chosen as the dependent variables.
Results mSCORE was directly related to the age, disease duration, smoking habits and blood fat profile (cholesterol and triglycerides). These parameters were higher in the group with mSCORE≥1 (n=96) indicative for the increased cardiovascular risk. The patients with mSCORE≥1 had significantly higher levels of leptin (p=0.007), and resistin (p=0.03), while the levels of IGF-1 were significantly lower (p<0.0001) compared to the patients with lower cardiovascular risk (mSCORE<1, n=91). The overall transcriptional activity of the fat tissue adipocytes was prominently higher compared to peripheral blood leucocytes in patients with mSCORE≥1. In patients with mSCORE≥1, the relative transcription of RELA, AKT1 and TLR4 was higher compared to the patients with mSCORE<1.
The logistic regression analysis with mSCORE as a dependent variable showed that high serum levels of resistin and leptin were independently associated with the increased cardiovascular risk. Similar associations were observed for adipocyte expression of resistin-triggering genes TLR4 (OR 1.15 [95% CI 1.01-2.15]; p=0.03) and STAT3 (OR 2.39 [95% CI 1.00-5.74]; p=0.05). The logistic regression model with high serum resistin as a dependent variable revealed an association to high transcription of STAT3 (OR 1.12 [95% CI 1.00-3.30]; p=0.02), and low transcription of AKT1 in leukocytes and in adipocytes.
Conclusions The results of our study indicate that transcriptional activity of subcutaneous adipose tissue in women with RA is associated with the increased cardiovascular risk. High transcriptional activity of resistin-triggering genes may be a sufficient force driving premature cardiovascular disease in RA patients.
Boström EA, Svensson M, Andersson S, Jonsson IM, Ekwall AK, Eisler T, Dahlberg LE, Smith U, Bokarewa MI. Resistin and insulin/insulin-like growth factor signaling in rheumatoid arthritis. Arthritis Rheum. 2011,63:2894-904
Tarkowski A, Bjersing J, Shestakov A, Bokarewa MI. Resistin competes with lipopolysaccharide for binding to toll-like receptor 4. J Cell Mol Med. 2010,14:1419-31.
Disclosure of Interest None declared
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