Hyperphosphatemia Drives Procoagulant Microvesicle Generation in the Rat Partial Nephrectomy Model of CKD
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 vitr...
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MDPI AG
2020-11-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/9/11/3534 |
| _version_ | 1797549113362874368 |
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| author | Nima Abbasian Alison H. Goodall James O. Burton Debbie Bursnall Alan Bevington Nigel J. Brunskill |
| author_facet | Nima Abbasian Alison H. Goodall James O. Burton Debbie Bursnall Alan Bevington Nigel J. Brunskill |
| author_sort | Nima Abbasian |
| collection | DOAJ |
| description | 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, <i>p</i> < 0.0001) with elevated total plasma MVs (2.24 ± 0.37 versus 1.31 ± 0.24 × 10<sup>8</sup> per ml, <i>p</i> < 0.01), showing increased CD144 expression (145 ± 25% of control value, <i>p</i> < 0.0001), and enhanced procoagulant activity (18.06 ± 1.75 versus 4.99 ± 1.77 nM peak thrombin, <i>p</i> < 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. |
| first_indexed | 2024-03-10T15:09:53Z |
| format | Article |
| id | doaj.art-848a9b166665490cac04d0df82ed4b03 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T15:09:53Z |
| publishDate | 2020-11-01 |
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| series | Journal of Clinical Medicine |
| spelling | doaj.art-848a9b166665490cac04d0df82ed4b032023-11-20T19:26:00ZengMDPI AGJournal of Clinical Medicine2077-03832020-11-01911353410.3390/jcm9113534Hyperphosphatemia Drives Procoagulant Microvesicle Generation in the Rat Partial Nephrectomy Model of CKDNima Abbasian0Alison H. Goodall1James O. Burton2Debbie Bursnall3Alan Bevington4Nigel J. Brunskill5Department of Cardiovascular Sciences, University of Leicester, and Leicester NIHR Cardiovascular Biomedical Research Unit, Leicester LE3 9QP, UKDepartment of Cardiovascular Sciences, University of Leicester, and Leicester NIHR Cardiovascular Biomedical Research Unit, Leicester LE3 9QP, UKDepartment of Cardiovascular Sciences, University of Leicester, and Leicester NIHR Cardiovascular Biomedical Research Unit, Leicester LE3 9QP, UKDivision of Biomedical Services, University of Leicester, Leicester LE1 7RH, UKDepartment of Cardiovascular Sciences, University of Leicester, and Leicester NIHR Cardiovascular Biomedical Research Unit, Leicester LE3 9QP, UKDepartment of Cardiovascular Sciences, University of Leicester, and Leicester NIHR Cardiovascular Biomedical Research Unit, Leicester LE3 9QP, UKHyperphosphatemia 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, <i>p</i> < 0.0001) with elevated total plasma MVs (2.24 ± 0.37 versus 1.31 ± 0.24 × 10<sup>8</sup> per ml, <i>p</i> < 0.01), showing increased CD144 expression (145 ± 25% of control value, <i>p</i> < 0.0001), and enhanced procoagulant activity (18.06 ± 1.75 versus 4.99 ± 1.77 nM peak thrombin, <i>p</i> < 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.https://www.mdpi.com/2077-0383/9/11/3534hyperphosphatemiachronic kidney diseasecardiovascular diseaseendothelial cellsprocoagulant MVs |
| spellingShingle | Nima Abbasian Alison H. Goodall James O. Burton Debbie Bursnall Alan Bevington Nigel J. Brunskill Hyperphosphatemia Drives Procoagulant Microvesicle Generation in the Rat Partial Nephrectomy Model of CKD Journal of Clinical Medicine hyperphosphatemia chronic kidney disease cardiovascular disease endothelial cells procoagulant MVs |
| title | Hyperphosphatemia Drives Procoagulant Microvesicle Generation in the Rat Partial Nephrectomy Model of CKD |
| title_full | Hyperphosphatemia Drives Procoagulant Microvesicle Generation in the Rat Partial Nephrectomy Model of CKD |
| title_fullStr | Hyperphosphatemia Drives Procoagulant Microvesicle Generation in the Rat Partial Nephrectomy Model of CKD |
| title_full_unstemmed | Hyperphosphatemia Drives Procoagulant Microvesicle Generation in the Rat Partial Nephrectomy Model of CKD |
| title_short | Hyperphosphatemia Drives Procoagulant Microvesicle Generation in the Rat Partial Nephrectomy Model of CKD |
| title_sort | hyperphosphatemia drives procoagulant microvesicle generation in the rat partial nephrectomy model of ckd |
| topic | hyperphosphatemia chronic kidney disease cardiovascular disease endothelial cells procoagulant MVs |
| url | https://www.mdpi.com/2077-0383/9/11/3534 |
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