| Autor: |
Vila Cuenca M; 1 Department of Nephrology VU University Medical Center Amsterdam The Netherlands.; 2 Amsterdam Cardiovascular Sciences Amsterdam The Netherlands., Ferrantelli E; 3 Department of Molecular Cell Biology and Immunology VU University Medical Center Amsterdam The Netherlands., Meinster E; 4 Department of Pathology and Cardiac Surgery VU University Medical Center Amsterdam The Netherlands., Pouw SM; 3 Department of Molecular Cell Biology and Immunology VU University Medical Center Amsterdam The Netherlands., Kovačević I; 2 Amsterdam Cardiovascular Sciences Amsterdam The Netherlands.; 5 Department of Physiology VU University Medical Center Amsterdam The Netherlands., de Menezes RX; 6 Department of Epidemiology and Biostatistics VU University Medical Center Amsterdam The Netherlands., Niessen HW; 2 Amsterdam Cardiovascular Sciences Amsterdam The Netherlands.; 4 Department of Pathology and Cardiac Surgery VU University Medical Center Amsterdam The Netherlands., Beelen RHJ; 3 Department of Molecular Cell Biology and Immunology VU University Medical Center Amsterdam The Netherlands., Hordijk PL; 2 Amsterdam Cardiovascular Sciences Amsterdam The Netherlands.; 5 Department of Physiology VU University Medical Center Amsterdam The Netherlands., Vervloet MG; 1 Department of Nephrology VU University Medical Center Amsterdam The Netherlands.; 2 Amsterdam Cardiovascular Sciences Amsterdam The Netherlands. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of the American Heart Association [J Am Heart Assoc] 2018 Sep 04; Vol. 7 (17), pp. e008776. |
| DOI: |
10.1161/JAHA.118.008776 |
| Abstrakt: |
Background Dysfunctional endothelium may contribute to the development of cardiovascular complications in chronic kidney disease ( CKD ). Supplementation with active vitamin D has been proposed to have vasoprotective potential in CKD , not only by direct effects on the endothelium but also by an increment of α-Klotho. Here, we explored the capacity of the active vitamin D analogue paricalcitol to protect against uremia-induced endothelial damage and the extent to which this was dependent on increased α-Klotho concentrations. Methods and Results In a combined rat model of CKD with vitamin D deficiency, renal failure induced vascular permeability and endothelial-gap formation in thoracic aorta irrespective of baseline vitamin D, and this was attenuated by paricalcitol. Downregulation of renal and serum α-Klotho was found in the CKD model, which was not restored by paricalcitol. By measuring the real-time changes of the human endothelial barrier function, we found that paricalcitol effectively improved the recovery of endothelial integrity following the addition of the pro-permeability factor thrombin and the induction of a wound. Furthermore, immunofluorescence staining revealed that paricalcitol promoted vascular endothelial-cadherin-based cell-cell junctions and diminished F-actin stress fiber organization, preventing the formation of endothelial intracellular gaps. Conclusions Our results demonstrate that paricalcitol attenuates the CKD -induced endothelial damage in the thoracic aorta and directly mediates endothelial stability in vitro by enforcing cell-cell interactions. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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