Abstract
Elevated systemic pentraxin 3 (PTX3) levels appear to be a powerful marker of inflammatory status and a superior outcome predictor in patients with chronic kidney disease (CKD). As previous data imply that PTX3 is involved in vascular pathology and that adipose tissue mass may influence circulating PTX3 levels, we aimed to study the importance of adipose tissue expression of PTX3 in the uremic milieu and its relation to endothelial dysfunction parameters. Plasma PTX3 and abdominal subcutaneous adipose tissue (SAT) PTX3 mRNA levels were quantified in 56 stage 5 CKD patients (median age 57 [range 25–75] years, 30 males) and 40 age and gender matched controls (median age 58 [range 20–79] years, 27 males). Associations between PTX3 measures and an extensive panel of clinical parameters, including surrogate markers of endothelial function, were assessed. Functional ex vivo studies on endothelial status and immunohistochemical staining for PTX3 were conducted in resistance subcutaneous arteries isolated from SAT. SAT PTX3 mRNA expression correlated with plasma PTX3 concentrations (rho = 0.54, p = 0.0001) and was increased (3.7 [0.4–70.3] vs. 1.2 [0.2–49.3] RQ, p = 0.02) in CKD patients with cardiovascular disease (CVD), but was not significantly different between patients and controls. The association to CVD was lost after adjustments. SAT PTX3 mRNA levels were independently correlated to asymmetric dimethylarginine and basal resistance artery tone developed after inhibition with nitric oxide synthase and cyclooxygenase (rho = −0.58, p = 0.002). Apparent positive PTX3 immunoreactivity was observed in both patient and control arteries. In conclusion, fat PTX3 mRNA levels are associated with measures of endothelial cell function in patients with CKD. PTX3 may be involved in adipose tissue-orchestrated mechanisms that are restricted to the uremic milieu and modify inflammation and vascular complications in CKD patients.
Highlights
Endothelial dysfunction is a common feature in the uremic milieu [1], which predicts cardiovascular events and poor outcome in patients with chronic kidney disease (CKD) [2]
Univariate analyses showed that plasma PTX3 and PTX3 mRNA expression were positively correlated in patients (Table 2), but not in the non-CKD controls
We report that only patients with CKD show an association between subcutaneous adipose tissue (SAT) PTX3 mRNA and plasma PTX3 levels, despite similar SAT PTX3 mRNA levels in patients and non-CKD controls
Summary
Endothelial dysfunction is a common feature in the uremic milieu [1], which predicts cardiovascular events and poor outcome in patients with chronic kidney disease (CKD) [2]. CKD patients run a markedly increased cardiovascular disease (CVD) risk [3], these complications are often underdiagnosed and undertreated in this population. The presence of endothelial dysfunction is linked to inflammation [4], which has repeatedly been shown to enhance the risk for CVD mortality in both renal [5] and non-renal populations [6]. CKD patients seem to be prone to develop persistent inflammation, potentially due to raised production as well as decreased renal clearance of pro-inflammatory cytokines [7]. Beyond its expanding importance as an inflammatory marker, PTX3 possesses numerous additional regulatory functions, including effects on angiogenesis, atherosclerotic lesion development, apoptopic cell clearance, tissue repair and regulation of renal immunopathology [9]. In contrast to short pentraxins (such as CRP), which are only expressed by hepatocytes, PTX3 is produced at the actual site of inflammation
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