Association of plasma soluble E-selectin and adiponectin with carotid plaque in patients with systemic lupus erythematosus

Abstract

Background Systemic lupus erythematosus (SLE) is associated with premature atherosclerosis but the mechanisms underlying this association are not understood. The role of endothelial dysfunction is hypothesized. Methods In predominantly non-Caucasian patients with SLE (n=119) and controls (n=71), carotid ultrasonography was performed and circulating endothelial cells (CECs), soluble endothelial protein C receptor and gene polymorphism at A6936G, soluble E-selectin (sE-selectin), and adiponectin were assessed. Results Carotid plaque was more prevalent among patients than controls (43% vs 17%, p = 0.0002). Mean CCA IMT was greater in patients compared to controls (0.59mm ± 0.19 vs 0.54mm ± 0.11, p=0.03). Among SLE patients, plaque was not associated with smoking, body mass index, LDL, triglycerides, homocysteine, C-reactive protein, anti-ds DNA antibody, C3, C4, SLE activity, or medications. Age and levels of soluble E-selectin and adiponectin were significantly higher in the SLE patients with plaque compared to those without plaque in univariate and multivariate analyses. sE-selectin and adiponectin were found to serve as independent predictors of carotid plaque and that elevations were persistent over more than one visit. Unexpectedly, these biomarkers were present despite clinical quiescence. Conclusion Premature atherosclerosis is a consistent feature of SLE and extends across ethnicities. Higher levels of adiponectin may represent a physiological attempt to limit further endothelial damage already reflected by the elevation in sE-selectin and the observed increase in plaque represents overwhelming of this reparative process by atherogenic stimuli.

Subclinical Atherosclerosis in Systemic Autoimmune Disorders

“…Insulin resistance per se as defined by the WHO criteria was more prevalent in lupus patients compared to controls (44.1% versus 24.8%) (Chung, Avalos et al 2007). Similarly to RA, increased levels of adiponectin have been reported in SLE patients (Sada, Yamasaki et al 2006;Chung, Long et al 2009;Vadacca, Margiotta et al 2009) and found to be associated with carotid plaque formation, as a physiologic attempt to limit endothelial damage (Sada, Yamasaki et al 2006;Vadacca, Margiotta et al 2009;Clancy and Ginzler 2010;Reynolds, Buyon et al 2010). Opposite are the findings reported by Chung et al, where lower levels of adiponectin were associated with insulin resistance, BMI and CRP but not with coronary atherosclerosis (Chung, Long et al 2009).…”

Cardiometabolic comorbidities and rheumatic diseases: Focus on the role of fat mass and adipokines

“…In contrast, other authors did not find any difference in adiponectin levels between SLE patients and controls (53,54). Interestingly, adiponectin levels are increased in SLE patients with carotid plaques (106) and in renal SLE-associated vasculopathy (107).…”

Meta-analysis of Circulating Adiponectin, Visfatin, and Ghrelin Levels in Patients with Systemic Lupus Erythematosus

“…Adiponectin were significantly higher in the SLE patients with plaque compared to those without plaque in multivariate analysis, indicating that adiponectin may serve as independent predictor of carotid plaque [15]. Adiponectin was negatively associated with BMI, insulin resistance (IR) and C-reactive protein (ρ=−0.40, p＜0.001; ρ= −0.38, p＜0.001; ρ=−0.22, p=0.02, respectively) [17,18], and ghrelin levels correlate with homocysteine [18].…”

“…Sixteen studies were selected for full-text review based on the title and abstract, but five of these were excluded because they were a review or had no data on the adipokine levels. Finally, 11 articles met the inclusion criteria for this meta-analysis ( Figure 1) [12][13][14][15][16][17][18][19][20][21][22]. Three of the eligible studies included data on two different groups [13,18,20] that were treated independently.…”

“…Ghrelin exerts multiple immunoregulatory effects by antagonizing leptin [11]. Studies on circulating adiponectin, visfatin, and ghrelin levels in patients with SLE compared to healthy controls have shown mixed results [12][13][14][15][16][17][18][19][20][21][22]. The reasons for such disparity may be the small sample size, low statistical power, and/or clinical heterogeneity [23][24][25].…”