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Markers of endothelial glycocalyx dysfunction in Clarkson disease

ABSTRACT: Background Clarkson disease is a rare idiopathic condition marked by transient, relapsing-remitting episodes of systemic microvascular hyper-permeability, which liberates plasma fluid and macromolecules into the peripheral tissues. This pathology manifests clinically as the abrupt onset of hypotensive shock, he-moconcentration, and hypoalbuminemia. Methods We analysed endothelial glycocalyx (eGCX)-related markers in plasma from patients with SCLS dur-ing acute disease flares and convalescence by ELISA and comprehensive proteomic profiling. eGCX-related components and gene expression in cultured endothelial cells were evaluated by RNA-sequencing, real-time PCR, and fluorescence. Results Serum levels of eGCX-related core components including hyaluronic acid (HA) and/or the core pro-teoglycan soluble syndecan-1 (sCD138) were elevated at baseline and during acute SCLS flares. Se-rial measurements in several patients demonstrated that sCD138 levels peaked during the recovery (post-leak) phase of the illness. Proteomic analysis of matched acute and convalescent SCLS plasma revealed increased abundance of eGCX-related proteins, including glypicans, thrombospondin-1 (TSP-1), and eGCX-degrading enzymes in acute plasma compared to remission plasma. Abundance of endothelial cell damage markers did not differ in acute and baseline plasma. Expression of several eGCX-related genes and surface carbohydrate content in endothelial cells from patients with SCLS did not differ significantly from that observed in healthy control cells. Conclusions eGCX dysfunction, but not endothelial injury, may contribute to clinical symptoms of acute SCLS. Serum levels of of eGCX components including sCD138 may be measured during acute episodes of SCLS to monitor clinical status and therapeutic responses.

ORGANISM(S): Homo sapiens

PROVIDER: GSE204882 | GEO | 2022/05/29

REPOSITORIES: GEO

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Project description:Exercise has multi-systemic benefits and attenuates the physiological impairments associated with aging. Emerging evidence suggests that circulating exosomes mediate some of the beneficial effects of exercise via the transfer of microRNAs between tissues. However, the impact of regular exercise and acute exercise on circulating exosomal microRNAs (exomiRs) in older populations remains unknown. In the present study, we analyzed circulating exomiR expression in endurance-trained elderly men and age-matched sedentary males at baseline (Pre), immediately after a forty minute bout of aerobic exercise on a cycle ergometer (Post), and three hours after this acute exercise (3hPost). Plasma exosomes were isolated, characterized, and exomiR levels were determined by sequencing. The effect of regular exercise on circulating exomiRs was assessed using paired t-tests of baseline expression levels in the trained and sedentary groups. The effect of acute exercise was determined by comparing baseline and post-training expression levels in each group. Regular exercise resulted in significantly increased baseline expression of three exomiRs (miR-486-5p, miR-215-5p, miR-941) and decreased expression of one exomiR (miR-151b). Acute exercise altered circulating exomiR expression in both groups. However, exomiRs regulated by acute exercise in the trained group (7 miRNAs at Post and 8 at 3hPost) were distinct from those in the sedentary group (9 at Post and 4 at 3hPost). Pathway analysis prediction and reported target validation experiments revealed that the majority of exercise-regulated exomiRs are targeting genes that are related to IGF-1 signaling, a pathway involved in exercise-induced muscle and cardiac hypertrophy. The immediately post-acute exercise exomiR signature in the trained group correlates with activation of IGF-1 signaling, whereas in the sedentary group it is associated with inhibition of IGF-1 signaling. These results suggest that training status may counteract age-related anabolic resistance by modulating circulating exomiR profiles both at baseline and in response to acute exercise.

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Markers of endothelial glycocalyx dysfunction in Clarkson disease

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