Vitamin D Attenuates Endothelial Dysfunction in Uremic Rats and Maintains Human Endothelial Stability

• Published in: Journal of the American Heart Association Vol. 7; no. 17; p. e008776
• Main Authors: Vila Cuenca, Marc, Ferrantelli, Evelina, Meinster, Elisa, Pouw, Stephan M, Kovačević, Igor, de Menezes, Renee X, Niessen, Hans W, Beelen, Robert H J, Hordijk, Peter L, Vervloet, Marc G
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 04.09.2018; Wiley
• Subjects: chronic kidney disease; endothelial dysfunction; Klotho; Original Research; vitamin D; chronic kidney disease; Klotho; endothelial dysfunction; vitamin D
• ISSN: 2047-9980; 2047-9980
• DOI: 10.1161/JAHA.118.008776

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.