Degradation of endothelial glycocalyx in Tanzanian children with falciparum malaria.

Degradation of endothelial glycocalyx in Tanzanian children with falciparum malaria.
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坦桑尼亚恶性疟患儿内皮糖萼的降解。

DOI:
10.1096/fj.202100277rr
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发表时间:
2021-09
期刊:
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子:
--
通讯作者:
Weinberg JB
Weinberg JB
中科院分区:
其他
文献类型:
--
作者:
Bush MA;Florence SM;Yeo TW;Kalingonji AR;Chen Y;Granger DL;Rubach MP;Anstey NM;Mwaikambo ED;Weinberg JB

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一层糖萼覆盖着血管内皮,起着重要的保护和稳态功能。本研究的目的是确定在儿童疟疾感染期间是否发生内皮糖萼(eGC)的破坏。在146名儿童中前瞻性地评估了eGC完整性、内皮活化和微血管反应性的测量:44名中重度疟疾(MSM)、42名重度疟疾(SM)和60名健康对照(HC)。eGC完整性的生化测量包括血浆多配体蛋白聚糖-1和总尿糖胺聚糖(GAG)。侧流暗场成像用于定量评估eGC的完整性。测量血浆血管生成素-2(Ang-2)作为内皮活化的标志物,也作为eGC分解的可能介质。我们的研究结果表明,尿GAG,syndecan-1,和Ang-2升高与MSM和SM患者相比,HC。Syndecan-1和GAG水平彼此显著相关,并与血浆Ang-2显著相关。eGC分解产物还与血红蛋白和血小板计数显著负相关。在MSM组中,成像结果为eGC降解提供了进一步的证据。虽然与eGC降解标志物无关,但血管功能[通过无创近红外光谱(NIRS)评估]显示微血管反应性降低,特别是影响SM组。我们的研究结果为恶性疟疾中eGC的分解提供了进一步的证据,这可能有助于内皮激活和寄生红细胞的粘附,减少一氧化氮的形成和血管功能障碍。
A layer of glycocalyx covers the vascular endothelium serving important protective and homeostatic functions. The objective of this study was to determine if breakdown of the endothelial glycocalyx (eGC) occurs during malaria infection in children. Measures of eGC integrity, endothelial activation, and microvascular reactivity were prospectively evaluated in 146 children: 44 with moderately severe malaria (MSM), 42 with severe malaria (SM), and 60 healthy controls (HC). Biochemical measures of eGC integrity included plasma syndecan-1 and total urinary glycosaminoglycans (GAG). Side-stream dark field imaging was used to quantitatively assess integrity of eGC. Plasma angiopoietin-2 (Ang-2) was measured as a marker of endothelial activation and also as a possible mediator of eGC breakdown. Our results show that urinary GAG, syndecan-1, and Ang-2 were elevated in patients with MSM and SM compared with HC. Syndecan-1 and GAG levels correlated significantly with each other and with plasma Ang-2. The eGC breakdown products also inversely correlated significantly with hemoglobin and platelet count. In the MSM group, imaging results provided further evidence for eGC degradation. Although not correlated with markers of eGC degradation, vascular function [assessed by non-invasive near infrared spectroscopy (NIRS)] demonstrated reduced microvascular reactivity, particularly affecting the SM group. Our findings provide further evidence for breakdown of eGC in falciparum malaria that may contribute to endothelial activation and adhesion of parasitized RBC, with reduced nitric oxide formation, and vascular dysfunction.
坦桑尼亚儿童的严重和简单恶性疟疾的坦桑尼亚儿童的微血管功能降低。
DOI: 10.1093/ofid/ofx079
发表时间: 2017
影响因子: 4.2
作者:
Yeo TW;Florence SM;Kalingonji AR;Chen Y;Granger DL;Anstey NM;Mwaikambo ED;Weinberg JB
通讯作者: Weinberg JB