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CXCL9 and its Receptor CXCR3, an Important Link Between Inflammation and Cardiovascular Risks in RA Patients
Afsaneh Shamsi1, Seyed Askar Roghani1,2,3, Zahra Abdan3
1Immunology Department, Faculty of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Insights
Inflammation markers CXCL9 and CXCR3 gene expression are elevated in rheumatoid arthritis (RA) patients, correlating with cardiovascular disease (CVD) risk factors. This highlights their potential role in RA-associated CVD pathogenesis.
Area of Science:
- Immunology and Rheumatology
- Cardiovascular Medicine
Background:
- Cardiovascular disease (CVD) is a leading cause of mortality in rheumatoid arthritis (RA).
- Inflammation plays a critical role in the pathogenesis of both RA and CVD.
- Chemokine (C-X-C motif) ligand 9 (CXCL9) is implicated in inflammatory processes contributing to CVD.
Purpose of the Study:
- To investigate the association between plasma CXCL9, CXCR3 gene expression, and cardiovascular risk factors in RA patients.
- To evaluate the relationship of these markers with RA disease activity and established CVD risk scores.
Main Methods:
- Study included 30 newly diagnosed RA patients, 30 on-treatment RA patients, and 30 healthy controls.
- Plasma CXCL9 levels were measured by ELISA.
- CXCR3 gene expression was quantified using Real-Time PCR.
- Cardiovascular risk was assessed using Framingham Risk Score (FRS) and Systematic Coronary Risk Evaluation (SCORE).
Main Results:
- Plasma CXCL9 and CXCR3 gene expression were significantly elevated in both newly diagnosed and on-treatment RA patients compared to controls.
- Both CXCL9 and CXCR3 showed significant positive correlations with RA disease activity.
- CXCR3 gene expression correlated with age, systolic blood pressure, FRS, and SCORE.
- Plasma CXCL9 negatively correlated with HDL and LDL cholesterol levels.
Conclusions:
- Elevated CXCL9 and CXCR3 are associated with increased cardiovascular risk factors in RA patients.
- These findings suggest a potential role for CXCL9 and CXCR3 in the pathogenesis of CVD in the context of RA.
- Further research is warranted to explore therapeutic strategies targeting these pathways.
Abstract:
Cardiovascular disease (CVD) is the most common cause of mortality in rheumatoid arthritis (RA), and Inflammation has a decisive role in its pathogenesis. CXCL9 contributes to multi aspects of inflammatory reactions associated with the pathogenesis of CVD. In the current study, we evaluated the association of plasma CXCL9 and CXCR3 gene expression with Cardiovascular risk factors in RA patients for the first time. Thirty newly diagnosed, 30 on-treatment RA patients, and 30 healthy subjects were recruited in this study. The plasma concentration of CXCL9 and CXCR3 gene expression were measured using ELISA and Real-Time PCR, respectively. The CVD risk was evaluated using Framingham Risk Score (FRS) and Systematic Coronary Risk Evaluation (SCORE). The plasma levels of CXCL9 were significantly higher in the newly diagnosed and on-treatment RA patients compared to the control group (P < 0.0001 and P < 0.001, respectively). Also, The CXCR3 gene expression was strongly elevated in newly diagnosed and on-treatment patients (P < 0.001 and P < 0.01, respectively). The CXCL9 and CXCR3 were significantly associated with RA disease activity (P = 0.0005, r = 0.436; P = 0.0002, r = 0.463, respectively). The FRS was remarkably higher in newly diagnosed and on-treatment patients (P = 0.014 and P = 0.035, respectively). The CXCR3 gene expression significantly correlated with age, systolic blood pressure, FRS, and SCORE (P = 0.020, r = 0.298; P = 0.006, r = 0.346; P = 0.006, r = 0.349; P = 0.007, r = 0.341, respectively). The CXCL9 plasma concentration had a significant negative correlation with plasma HDL and LDL levels (P = 0.033, r = -0.275; P = 0.021, r = -0.296, respectively). CXCL9 and CXCR3 correlates with different variables of CVD in RA.
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