Uremia Impacts VE-Cadherin and ZO-1 Expression in Human Endothelial Cell-to-Cell Junctions
| Autor: | Paulo Gregório, Célia Regina Cavichiolo Franco, Carla J. Dolenga, Lia S. Nakao, Ziad A. Massy, Roberto Pecoits-Filho, Regiane Stafim da Cunha, Andréa E.M. Stinghen, Agnès Boullier, Valentina Busato, Rayana Ariane Pereira Maciel |
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| Přispěvatelé: | Hôpital Ambroise Paré [AP-HP], Épidémiologie et recherches translationnelles sur les maladies rénales et cardiovasculaires (EPREC) (U1018 (Équipe 5)), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Health Toxicology and Mutagenesis [SDV]Life Sciences [q-bio] uremic toxins 030232 urology & nephrology lcsh:Medicine Sulfuric Acid Esters Toxicology Cell junction Article Cell Line Phosphates 03 medical and health sciences Cresols 0302 clinical medicine Renal Artery Antigens CD Internal medicine medicine Humans Endothelial dysfunction Renal Insufficiency Chronic Toxins Biological Uremia business.industry lcsh:R Endothelial Cells Middle Aged medicine.disease Cadherins In vitro Pathophysiology Endothelial stem cell 030104 developmental biology Endocrinology Intercellular Junctions Zonula Occludens-1 Protein Female VE-cadherin business Indican chronic kidney disease Kidney disease |
| Zdroj: | Toxins Toxins, Vol 10, Iss 10, p 404 (2018) Volume 10 Issue 10 Toxins, MDPI, 2018, 10 (10), ⟨10.3390/toxins10100404⟩ |
| ISSN: | 2072-6651 |
| Popis: | 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&rsquo 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. |
| Databáze: | OpenAIRE |
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