Divisions of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
PLoS One. 2013 May 3;8(5):e63493. doi: 10.1371/journal.pone.0063493. Print 2013.
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.
升高的系统 pentraxin 3（PTX3）水平似乎是慢性肾脏病（CKD）患者炎症状态的有力标志物和预后预测因子。由于先前的数据表明 PTX3 参与血管病理学，并且脂肪组织质量可能影响循环 PTX3 水平，因此我们旨在研究尿毒症环境中脂肪组织 PTX3 的表达及其与内皮功能障碍参数的关系。在 56 名 5 期 CKD 患者（中位年龄 57 [范围 25-75] 岁，30 名男性）和 40 名年龄和性别匹配的对照组（中位年龄 58 [范围 20-79] 岁，27 名男性）中定量检测了血浆 PTX3 和腹部皮下脂肪组织（SAT）PTX3 mRNA 水平。评估了 PTX3 测量值与广泛的临床参数（包括内皮功能的替代标志物）之间的关联。对从 SAT 分离的阻力皮下动脉进行了内皮状态的体外功能研究和 PTX3 的免疫组织化学染色。SAT PTX3 mRNA 表达与血浆 PTX3 浓度相关（rho = 0.54，p = 0.0001），并且在患有心血管疾病（CVD）的 CKD 患者中增加（3.7 [0.4-70.3] 与 1.2 [0.2-49.3] RQ，p = 0.02），但在患者和对照组之间无显着差异。调整后，与 CVD 的关联消失。SAT PTX3 mRNA 水平与不对称二甲基精氨酸独立相关，并与一氧化氮合酶和环氧化酶抑制后基底阻力动脉张力相关（rho = -0.58，p = 0.002）。在患者和对照组的动脉中均观察到明显的阳性 PTX3 免疫反应性。总之，CKD 患者的脂肪 PTX3 mRNA 水平与内皮细胞功能的测量值相关。PTX3 可能参与受尿毒症限制并改变 CKD 患者炎症和血管并发症的脂肪组织协调机制。
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