Ulrich Christof, Trojanowicz Bogusz, Fiedler Roman, Kohler Felix, Wolf Anna-Franziska, Seibert Eric, Girndt Matthias
Department of Internal Medicine II, Martin Luther University Halle-Wittenberg, Halle, Germany.
Nephron. 2017;135(3):231-241. doi: 10.1159/000454778. Epub 2016 Dec 20.
Monocytic products, such as lipoprotein-associated phospholipase A2 (Lp-PLA2), may participate in the development of atherosclerosis. Heterogeneity of monocytes is widely acknowledged. Classical, intermediate, and non-classical subsets can be discerned. Recently, an inflammatory, pro-atherogenic monocyte population could be identified in hemodialysis patients. In this study, we investigated the expression of Lp-PLA2 on leucocytes and different monocyte subpopulations and their possible role in uremia, inflammation, and atherosclerosis.
Chronic kidney disease stage 5-D (CKD5-D; n = 57), healthy control subjects with hs-C-reactive protein (CRP) levels ≤1 mg/L (CO-N, n = 22) and a control group with inflammatory activation (CRP levels >1 mg/L, CO-I, n = 29) were enrolled in this cross-sectional observation. The CKD5-D cohort was dichotomized into patients with (A+) and without subclinical atherosclerosis (A-) by carotid artery ultrasound measurement. Lp-PLA2 activity was determined in plasma samples, Lp-PLA2 mRNA expression analysis in leucocytes, and sorted monocyte subsets. Effects of Lp-PLA2 overexpression were studied in classical vs. intermediate and non-classical subsets.
The classical monocytes expressed the highest Lp-PLA2 mRNA levels as compared to other subpopulations. CKD5-D patients revealed significantly higher Lp-PLA2 transcripts, as well as higher Lp-PLA2 plasma activity as compared to healthy and "inflammatory" controls. In vitro data confirmed that uremia significantly contributes to Lp-PLA2 mRNA upregulation. Non-classical monocytes of A+ patients revealed significant higher Lp-PLA2 mRNA compared to A-.
Uremic environment but not inflammation per se increases plasma Lp-PLA2 activity and upregulates monocytic Lp-PLA2 mRNA expression. The highest Lp-PLA2 levels were found in the classical and not in the inflammatory subsets. Atherosclerosis also contributes to a subset-specific increase in Lp-PLA2 mRNA expression.
单核细胞产物，如脂蛋白相关磷脂酶A2（Lp-PLA2），可能参与动脉粥样硬化的发展。单核细胞的异质性已得到广泛认可。可区分出经典型、中间型和非经典型亚群。最近，在血液透析患者中发现了一种具有炎症性、促动脉粥样硬化的单核细胞群体。在本研究中，我们调查了Lp-PLA2在白细胞和不同单核细胞亚群上的表达及其在尿毒症、炎症和动脉粥样硬化中的可能作用。
纳入慢性肾脏病5期透析患者（CKD5-D；n = 57）、hs-C反应蛋白（CRP）水平≤1 mg/L的健康对照者（CO-N，n = 22）以及炎症激活的对照组（CRP水平>1 mg/L，CO-I，n = 29）进行横断面观察。通过颈动脉超声测量将CKD5-D队列分为有亚临床动脉粥样硬化（A+）和无亚临床动脉粥样硬化（A-）的患者。测定血浆样本中的Lp-PLA2活性，分析白细胞及分选的单核细胞亚群中的Lp-PLA2 mRNA表达。研究Lp-PLA2过表达在经典型与中间型及非经典型亚群中的作用。
与其他亚群相比，经典单核细胞表达的Lp-PLA2 mRNA水平最高。与健康对照和“炎症”对照相比，CKD5-D患者的Lp-PLA2转录本显著更高，血浆Lp-PLA2活性也更高。体外数据证实尿毒症显著促进Lp-PLA2 mRNA上调。A+患者的非经典单核细胞与A-患者相比，Lp-PLA2 mRNA显著更高。
尿毒症环境而非炎症本身会增加血浆Lp-PLA2活性并上调单核细胞Lp-PLA2 mRNA表达。Lp-PLA2水平最高的是经典型而非炎症亚群。动脉粥样硬化也导致Lp-PLA2 mRNA表达出现亚群特异性增加。
