Serum Retinol-Binding Protein 4 as a Marker for Cardiovascular Disease in Women

Khalid M Alkharfy,Nasser M Al-Daghri,Soundararajan Krishnaswamy,Paul M Vanhoutte,Aimin Xu,Yu Wang

doi:10.1371/journal.pone.0048612

Khalid M Alkharfy, Nasser M Al-Daghri + Show 4 more

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https://doi.org/10.1371/journal.pone.0048612

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Abstract

BackgroundElevated serum level of retinol-binding protein 4 (RBP4) has been associated with obesity-related co-morbidities including insulin resistance, dyslipidemia and hypertension.ObjectivesThe present study examined the relationship between serum level of RBP4 and various risk factors related to cardiovascular disease (CVD) in men and women.Methods284 subjects (139 males, 145 females), grouped into healthy (n = 60), obese diabetes (n = 60), non-obese diabetes (n = 60), obese non-diabetes (n = 60) and patients with CVD (n = 44), were assessed for anthropometric and biochemical parameters related to obesity, diabetes and CVD. In addition, serum levels of several adipokines, including fatty acid binding protein 4 (FABP4) and lipocalin 2 (LCN2) and RBP4 were measured using specific immunoassays.ResultsSerum RBP4 level correlated significantly with principal component derived from known risk factors of CVD (β = 0.20±0.06, P = 0.002). Significance of this correlation was limited to women (β = 0.20±0.06, P = 0.002) and it persisted even after adjusting for BMI (β = 0.19±0.06, P = 0.002). Overall (n = 284) serum RBP4 values significantly correlated with FABP4 (R = 0.19, p = 0.001). Serum FABP4 level of CVD subjects was significantly higher than healthy control (P = 0.001) and non-obese diabetes (P = 0.04) groups, but this difference was attributable to differences in BMI. Serum LCN2 level correlated well with RBP4 (R = 0.15, P = 0.008) and FABP4 (R = 0.36, P<0.001), but did not differ significantly between CVD and other groups.ConclusionsResults of this study indicate a significant correlation between serum RBP4 and various established risk factors for CVD and suggest RBP4 may serve as an independent predictor of CVD in women.

Highlights

Cardiovascular diseases (CVD) are a principal cause of death worldwide and are linked to obesity and metabolic syndrome
Results of this study indicate a significant correlation between serum retinol-binding protein 4 (RBP4) and various established risk factors for CVD and suggest RBP4 may serve as an independent predictor of CVD in women
Since fatty acid binding protein 4 (FABP4), lipocalin 2 (LCN2) and RBP4 have been reported to relate to insulin resistance and metabolic syndrome, the serum values of these adipokines were measured in a Saudi population grouped into healthy control, obese without diabetes, non-obese diabetes, obese diabetes and subjects with CVD, to explore their potential as biomarkers for CVD (Figure 1)

Summary

Introduction

Cardiovascular diseases (CVD) are a principal cause of death worldwide and are linked to obesity and metabolic syndrome. The lipocalin family proteins, FABP4, LCN2 and RBP4, have been identified as adipokines associated with obesity, type 2 diabetes and metabolic syndrome. Epidemiological studies in different ethnic groups demonstrate a close association between serum levels of FABP4 and a cluster of obesity-related cardiometabolic risk factors [5,6,7,8,9]. Plasma FABP4 levels are positively correlated with measures of endothelial dysfunction [10], coronary atherosclerosis [11] and various types of cardiovascular diseases [9,12,13,14]. Elevated serum level of retinol-binding protein 4 (RBP4) has been associated with obesity-related comorbidities including insulin resistance, dyslipidemia and hypertension

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