In:
Nephron, S. Karger AG, Vol. 135, No. 3 ( 2017), p. 231-241
Abstract:
〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 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. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 Chronic kidney disease stage 5-D (CKD5-D; 〈 i 〉 n 〈 /i 〉 = 57), healthy control subjects with hs-C-reactive protein (CRP) levels ≤1 mg/L (CO-N, 〈 i 〉 n 〈 /i 〉 = 22) and a control group with inflammatory activation (CRP levels 〉 1 mg/L, CO-I, 〈 i 〉 n 〈 /i 〉 = 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. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 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-. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 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.
Type of Medium:
Online Resource
ISSN:
1660-8151
,
2235-3186
Language:
English
Publisher:
S. Karger AG
Publication Date:
2017
detail.hit.zdb_id:
2810853-X
