Uremia Impacts VE-Cadherin and ZO-1 Expression in Human Endothelial Cell-to-Cell Junctions

Rayana A. P. Maciel (1) , Regiane S. Cunha (1) , Valentina Busato (1) , Celia R. C. Franco (1) , Paulo C. Gregorio (1) , Carla J. R. Dolenga (1) , Lia S. Nakao (1) , Ziad A. Massy (2, 3) , Agnes Boullier (4, 5) , Roberto Pecoits-Filho (6) , Andrea E. M. Stinghen (1)

1 UFPR - Universidade Federal do Paraná [Curitiba, Brasil] = Federal University of Paraná [Curitiba, Brazil] = Université fédérale du Paraná [Curitiba, Brésil]
2 Hôpital Ambroise Paré [AP-HP]
3 CESP - Centre de recherche en épidémiologie et santé des populations
4 MP3CV - Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517
5 CHU Amiens-Picardie
6 PUCPR - Pontifícia Universidade Católica do Paraná [Curitiba, Brasil] = Pontifical Catholic University of Paraná [Curitiba, Brazil] = Université catholique pontificale du Paraná [Curitiba, Brésil]

Endothelial dysfunction in uremia can result in cell-to-cell junction loss and increased permeability, contributing to cardiovascular diseases (CVD) development. This study evaluated the impact of the uremic milieu on endothelial morphology and cell junction's proteins. We evaluated (i) serum levels of inflammatory biomarkers in a cohort of chronic kidney disease (CKD) patients and the expression of VE-cadherin and Zonula Occludens-1 (ZO-1) junction proteins on endothelial cells (ECs) of arteries removed from CKD patients during renal transplant; (ii) ECs morphology in vitro under different uremic conditions, and (iii) the impact of uremic toxins p-cresyl sulfate (PCS), indoxyl sulfate (IS), and inorganic phosphate (Pi) as well as of total uremic serum on VE-cadherin and ZO-1 gene and protein expression in cultured ECs. We found that the uremic arteries had lost their intact and continuous endothelial morphology, with a reduction in VE-cadherin and ZO-1 expression. In cultured ECs, both VE-cadherin and ZO-1 protein expression decreased, mainly after exposure to Pi and uremic serum groups. VE-cadherin mRNA expression was reduced while ZO-1 was increased after exposure to PCS, IS, Pi, and uremic serum. Our findings show that uremia alters cell-to-cell junctions leading to an increased endothelial damage. This gives a new perspective regarding the pathophysiological role of uremia in intercellular junctions and opens new avenues to improve cardiovascular outcomes in CKD patients.

Mots clés: chronic kidney disease; intercellular junctions; uremic toxins

Domaines: Sciences du Vivant [q-bio]

Rayana A. P. Maciel, Regiane S. Cunha, Valentina Busato, Celia R. C. Franco, Paulo C. Gregorio, et al.. Uremia Impacts VE-Cadherin and ZO-1 Expression in Human Endothelial Cell-to-Cell Junctions. Toxins, 2018, 10 (10), ⟨10.3390/toxins10100404⟩. ⟨hal-03568254⟩