Association of secreted frizzled-related protein 4 (SFRP4) expression in human epicardial adipose tissue with coronary atherosclerosis
Yu Du1 2 Qingwei Ji1 Yingxin Zhao1 2 Zhijian Wang1 Jianwei Zhang1 Yujie Zhou1 2
1.Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University
2.Beijing Institute of Heart Lung and Blood Vessel Diseases
Objectives: Association of circulating secreted frizzled-related protein 4 (SFRP4) and β-cell dysfunction, insulin resistance and other metabolic disorders has been widely studied. We aimed at investigating the association between SFRP4 expression in human epicardial adipose tissue (EAT) and coronary atherosclerosis.
Methods: Serum samples and adipose biopsies from EAT and subcutaneous adipose tissue (SAT) were collected from patients with and without coronary artery disease (CAD, n = 40 and non-CAD, n = 30, respectively) during elective cardiac surgery. CAD presence was identified by coronary angiography. SFRP4 mRNA and protein expressions in adipose tissue were detected by quantitative real-time PCR and immunohistochemistry, respectively. Serum SFRP4 concentrations were measured by ELISA. Correlation analysis and multivariate linear regression analysis were to determine the association of SFRP4 expression with atherosclerosis as well as clinical risk factors.
Results: SFRP4 mRNA and protein expressions were significantly lower in EAT than paired SAT in patients with and without CAD (all p < 0.05). Compared with non-CAD patients, CAD patients had higher SFRP4 expression in EAT (both mRNA and protein levels) and in serum. Multivariate linear regression analysis showed that CAD was an independent predictor for SFRP4 expression in EAT (beta = 0.442, 95% CI 0.030 – 0.814; p = 0.036) and in serum (beta = 0.300, 95% CI 0.056 – 0.545; p = 0.017). In addition, SAT derived SFRP4 mRNA levels were independently associated with fasting insulin levels (beta = 0.382, 95% CI 0.008 – 0.756; p = 0.045). Meanwhile, serum SFRP4 levels were positively correlated with BMI (r = 0.259, p = 0.030), fasting insulin levels (r = 0.306, p = 0.010) and HOMA-IR (r = 0.331, p = 0.005).
Conclusions: EAT-derived and circulating SFRP4 expressions were increased in patients with CAD. EAT SFRP4 mRNA levels and serum SFRP4 concentrations were independently associated with CAD presence, separately.