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Associations between the IL-6-neutralizing sIL-6R-sgp130 buffer system and coronary artery disease in postmenopausal
1Department of Clinical Laboratory, Wuhan University, Renmin Hospital, Wuhan 430060, China.
Insights
Biomarkers sgp130 and the B/T ratio in the IL-6 trans-signaling pathway show promise for diagnosing coronary artery disease (CAD) in postmenopausal women. Higher sgp130 levels independently predict lower CAD incidence.
Area of Science:
- Cardiovascular Biology
- Immunology
- Biomarker Discovery
Background:
- Interleukin-6 (IL-6) trans-signaling is a key inflammatory pathway implicated in coronary artery disease (CAD).
- This pathway is regulated by the balance between the IL-6:sIL-6Rα binary complex (B) and the IL-6:sIL-6Rα:sgp130 ternary complex (T).
- The IL-6-neutralizing sIL-6R-sgp130 buffer system plays a critical role in modulating this inflammatory process.
Purpose of the Study:
- To investigate the relationship between biomarkers of the IL-6-neutralizing sIL-6R-sgp130 buffer system and CAD in postmenopausal women.
- To assess the diagnostic and prognostic potential of these biomarkers for CAD.
- To evaluate the association of these biomarkers with the severity of coronary stenosis.
Main Methods:
- A case-control study involving 155 CAD patients and 181 postmenopausal controls.
- Measurement of circulating levels of IL-6, soluble IL-6 receptor alpha (sIL-6Rα), and soluble glycoprotein 130 (sgp130) using enzyme-linked immunosorbent assay.
- Calculation of the B/T ratio and correlation with Gensini scores for assessing coronary stenosis severity.
Main Results:
- CAD patients exhibited higher IL-6, sIL-6Rα, and B/T ratio, with lower sgp130 levels compared to controls.
- IL-6 and B/T ratio positively correlated with Gensini scores, while sgp130 negatively correlated.
- Higher sgp130 levels were an independent predictor of lower CAD incidence (OR=0.904; P=0.010), and specific cut-off points for sgp130 and B/T ratio effectively identified CAD presence.
Conclusions:
- sgp130 and the B/T ratio may serve as valuable biomarkers for CAD diagnosis in postmenopausal women.
- These biomarkers could aid in assessing the severity of coronary stenosis.
- Further validation in larger studies is warranted to confirm their clinical utility.
Background:
As a major inflammatory pathway in coronary artery disease (CAD), IL-6 trans-signaling is activated by the IL-6: sIL-6Rα binary complex (B) and inhibited by sgp130 through forming the IL-6: sIL-6Rα: sgp130 ternary complex (T). The aim of the present study was to examine the possible relationship between biomarkers mirroring the IL-6-neutralizing sIL-6R-sgp130 buffer system and CAD in postmenopausal women.
Methods:
Our study recruited 155 CAD patients and 181 controls among postmenopausal women. Circulating levels of IL-6, sIL-6Rα and sgp130 were detected using an enzyme-linked immunosorbent assay, and the B/T ratio was calculated by the specific formulas.
Results:
CAD patients showed significantly higher circulating levels of IL-6 and sIL-6Rα, significantly higher B/T ratio, and significantly lower sgp130 levels than controls (all P<0.05). Spearman's correlation analysis indicated that IL-6 levels (r=0.185, P<0.01) and B/T ratio (r=0.319, P<0.01) were positively related to Gensini scores, while elevated sgp130 levels were significantly associated with decreased Gensini scores (r=-0.565, P<0.001). In addition, multiple regression analysis showed that Gensini scores were negatively associated with serum sgp130 levels (β-coefficient =-0.318, P<0.001) and had a positive association with IL-6 levels (β-coefficient =0.138, P<0.05). Multivariate logistic regression analysis identified that after adjusting for confounding factors, higher sgp130 remained an independent predictor of lower incidence of CAD in women after menopause (OR =0.904; 95% CI: 0.837-0.976, P=0.010). Moreover, sgp130 levels at 136.01 ng/mL (AUC =0.957, 95% CI: 0.928-0.986, P<0.001) and B/T ratio at 1.51 (AUC =0.765; 95% CI: 0.702-0.828, P<0.001) were effective cut-off points to determine the presence of CAD based on receiver operating characteristic curves.
Conclusions:
Based on this small case-control study, sgp130 and B/T ratio in the IL-6-neutralizing sIL-6R-sgp130 buffer system may be promising biomarkers for CAD diagnosis and assessments of coronary stenosis severity in postmenopausal women.
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