24. Impact of immunosuppressive drugs on endothelial barrier

S.A. Nurmohamed, D. Ootes, P.L. Hordijk, M.G. Vervloet, J.W. van der Heijden, J.S.M. van Bezu

Thursday 5 march 2020

0:00 - 0:00h at Toon Hermans Foyer

Parallel session: Postersessie 6 – Basale abstracts

Background: Cardiovascular disease is still the major cause of death in renal transplant recipients. This group of patients has an extremely increased cardiovascular risk as compared to the general population with high prevalence of traditional and non-traditional risk factors. Both success and limitation of transplantation are primarily determined by the immunosuppressive medication. Apart from amplification of traditional risk factors, these drugs may also have a direct detrimental effect on endothelium. In this study we aim to investigate the effects of several immunosuppressive drugs on the endothelial barrier.

Methods: To analyze the effects of immunosuppressive drugs on the endothelial barrier function we used quantification of trans-endothelial electrical resistance using the Electrical Cell-substrate Impedance Sensing (ECIS) device. ECIS measurement was performed of human umbilical vein endothelial cells (HUVEC’s) pre-incubated with several drugs with different concentrations (prednisolon, cyclosporin, tacrolimus and everolimus). Regeneration of integrity after artificial electrical wounding was also measured. A comparison was made with a control condition.

Results: With the ECIS measurements tacrolimus seems to induce a concentration dependent improved barrier function as compared to the control condition. After wounding the tests also suggest an improved regeneration. Everolimus, however, seems to induce endothelial barrier dysfunction with disturbed regeneration after wounding. Cyclosporin did not show any effects on endothelium. Prednisolon revealed conflicting data.

Conclusions: Our data suggests the possibility of opposite effects of tacrolimus and everolimus on endothelial barrier function, Data validation, however, is necessary.