The relationship of novel adipokines, RBP4 and omentin-1, with carotid atherosclerosis severity and vulnerability
Introduction
Cerebral ischemia is one of the most important causes of morbidity and mortality in industrialized countries, associated with considerable medical and socio-economic burden [1]. Carotid artery stenosis as a causative factor of ischemic strokes or transient ischemic attacks (TIAs) constitutes a major therapeutic target of primary and secondary prevention strategies [2]. Randomized controlled trials and subsequent meta-analyses have demonstrated the degree of carotid stenosis as the gold-standard criterion for effective carotid revascularization in combination with best medical treatment in patients with symptoms (≥50% stenosis) and some selected patients without symptoms (≥80% stenosis) [3]. In addition to the magnitude of atherosclerosis, emerging evidence supports the prognostic power of plaque vulnerability in carotid atherosclerosis evolution [4]. Thereby, insights into the quantitative evaluation of both total plaque area (TPA) and texture would help to identify potentially high risk atherosclerotic lesions that would most benefit from intervention [5].
We know from numerous clinical and experimental trials that inflammation plays a pivotal role in the development and destabilization of carotid plaques [6], [7]. In vivo, the inflammatory process can easily be monitored by serum inflammatory biomarkers assay. Novel pro-inflammatory and anti-inflammatory derivatives from adipose tissue, known as adipokines, have recently been associated with carotid atherosclerosis [8]. Among them, retinol-binding protein 4 (RBP4) has emerged as a potential mediator of the interplay between obesity, insulin resistance, and inflammation [9], [10]. A growing body of evidence supports the positive relationship of RBP4 with the presence of either coronary artery disease (CAD) [11], [12] or subclinical carotid atherosclerosis [13]. However, the role of RBP4 in established carotid atherosclerosis is still obscure.
Another newly identified adipokine, omentin-1, has been intimately linked with protective mechanisms against obesity and insulin resistance [14]. Moreover, low plasma levels of omentin-1 have been measured in patients with extended CAD [15], or carotid atherosclerosis [16]. Nevertheless, no previous study has examined the interaction of omentin-1 with carotid atherosclerosis severity and vulnerability.
Taken together, the primary aim of the current study was to investigate the relationship of both RBP4 and omentin-1 serum levels with the presence and the ultrasonographically quantified severity of established carotid atherosclerosis. We also tested the hypothesis that these biomarkers correlate with ipsilateral neurological symptoms and valid ultrasound indices of plaque vulnerability.
Section snippets
Patients
In the present study we enrolled patients with established carotid atherosclerosis and individuals without current manifestations of atherosclerotic diseases. All participants underwent ultrasound examination of both carotids. Carotid atherosclerosis was characterized by the presence of at least one atherosclerotic plaque localized at the internal carotid artery (ICA) or the common carotid artery (CCA). Atherosclerotic plaque was defined as a focal structure encroaching into the arterial lumen
Comparison between established carotid atherosclerosis and controls
Results are depicted in Table 1. Patients with established carotid atherosclerosis showed significantly higher frequency of major cardiovascular risk factors, such as smoking habit, diabetes, hypertension and dyslipidemia, than individuals in the control group. Moreover, they appeared with higher concentrations of RBP4 and inflammatory markers (hsCRP and white blood cells count) (p < 0.05) and lower concentrations of omentin-1 (p < 0.001) than control counterparts.
Subgroup analysis revealed
Discussion
To our knowledge this is the first study evaluating the relationship of novel adipokines, RBP-4 and omentin-1, with ultrasonographically assessed carotid TPA and density. Our cross-sectional study showed significantly higher RBP4 and lower omentin-1 circulating levels in patients with carotid atherosclerosis compared to individuals without atherosclerotic manifestations. Moreover, serum RBP-4 levels were positively related to plaque area scoring (TPA), independent of traditional cardiovascular
Conflict of interest
All authors declare no conflict of interest.
Acknowledgments
Co-funded by the Operational Program “Competitiveness and Entrepreneurship” and Regional Operational Programmes of the National Strategic Reference Framework (NSRF) 2007-2013. “SYNERGASIA”: “Collaborative projects of small and medium scale” (09ΣΥΝ-12-1054).
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