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Hyperphosphatemia Drives Procoagulant Microvesicle Generation in the Rat Partial Nephrectomy Model of CKD.

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posted on 2020-11-24, 16:50 authored by Nima Abbasian, Alison H Goodall, James O Burton, Debbie Bursnall, Alan Bevington, Nigel J Brunskill
Hyperphosphatemia has been proposed as a cardiovascular risk factor, contributing to long-term vascular calcification in hyperphosphatemic Chronic Kidney Disease (CKD) patients. However, more recent studies have also demonstrated acute effects of inorganic phosphate (Pi) on endothelial cells in vitro, especially generation of pro-coagulant endothelial microvesicles (MV). Hitherto, such direct effects of hyperphosphatemia have not been reported in vivo. Thirty-six male Sprague-Dawley rats were randomly allocated to three experimental groups: (1) CKD induced by partial nephrectomy receiving high (1.2%) dietary phosphorus; (2) CKD receiving low (0.2%) dietary phosphorus; and (3) sham-operated controls receiving 1.2% phosphorus. After 14 days the animals were sacrificed and plasma MVs counted by nanoparticle tracking analysis. MVs isolated by centrifugation were assayed for pro-coagulant activity by calibrated automated thrombography, and relative content of endothelium-derived MVs was assessed by anti-CD144 immunoblotting. When compared with sham controls, high phosphorus CKD rats were shown to be hyperphosphatemic (4.11 ± 0.23 versus 2.41 ± 0.22 mM Pi, p < 0.0001) with elevated total plasma MVs (2.24 ± 0.37 versus 1.31 ± 0.24 × 108 per ml, p < 0.01), showing increased CD144 expression (145 ± 25% of control value, p < 0.0001), and enhanced procoagulant activity (18.06 ± 1.75 versus 4.99 ± 1.77 nM peak thrombin, p < 0.0001). These effects were abolished in the low phosphorus CKD group. In this rat model, hyperphosphatemia (or a Pi-dependent hormonal response derived from it) is sufficient to induce a marked increase in circulating pro-coagulant MVs, demonstrating an important link between hyperphosphatemia and thrombotic risk in CKD.

History

Citation

J. Clin. Med. 2020, 9(11), 3534; https://doi.org/10.3390/jcm9113534

Author affiliation

Department of Cardiovascular Sciences

Version

  • VoR (Version of Record)

Published in

Journal of clinical medicine

Volume

9

Issue

11

Pagination

3534 - 3534

Publisher

MDPI AG

issn

2077-0383

eissn

2077-0383

Acceptance date

2020-10-30

Copyright date

2020

Available date

2020-11-01

Spatial coverage

Switzerland

Language

eng

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