Oncotarget

Research Papers: Pathology:

This article has been corrected. Correction in: Oncotarget. 2017; 8(14):24045.

Nebivolol, a β1-adrenergic blocker, protects from peritoneal membrane damage induced during peritoneal dialysis

Georgios Liappas, Guadalupe González-Mateo, Anna Rita Aguirre, Hugo Abensur, Patricia Albar-Vizcaino, Emilio González Parra, Pilar Sandoval, Laura García Ramírez, Gloria del Peso, Juan Manuel Acedo, María A. Bajo, Rafael Selgas, José A. Sánchez Tomero, Manuel López-Cabrera _ and Abelardo Aguilera

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2016; 7:30133-30146. https://doi.org/10.18632/oncotarget.8780

Metrics: PDF 2182 views  |   HTML 3487 views  |   ?  


Abstract

Georgios Liappas1,*, Guadalupe González-Mateo1,*, Anna Rita Aguirre2,*, Hugo Abensur2, Patricia Albar-Vizcaino3, Emilio González Parra4, Pilar Sandoval1, Laura García Ramírez3, Gloria del Peso5, Juan Manuel Acedo6, María A. Bajo5, Rafael Selgas5, José A. Sánchez Tomero3, Manuel López-Cabrera1 and Abelardo Aguilera3

1 Immunology and Cellular Biology Department, Molecular Biology Centre Severo Ochoa, Madrid, Spain

2 Nephrology Department, University of Sao Paulo, School of Medicine, Sao Paulo, Brazil

3 Molecular Biology Unit and Nephrology Department, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain

4 Nephrology Department, Fundación Jiménez-Díaz, Instituto de Investigación Sanitaria, Madrid, Spain

5 Nephrology Department, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid, Spain

6 Cardiology Department, Clínica La Luz, Madrid, Spain

* These authors have contributed equally to the work

Correspondence to:

Manuel López-Cabrera, email:

Keywords: peritoneal dialysis, β-adrenergic receptor, nebivolol, type-I peritoneal membrane failure, peritoneal dialysis liquids, Pathology Section

Received: July 29, 2015 Accepted: March 31, 2016 Published: April 18, 2016

Abstract

Peritoneal dialysis (PD) is a form of renal replacement treatment, which employs the peritoneal membrane (PM) to eliminate toxins that cannot be removed by the kidney. The procedure itself, however, contributes to the loss of the PM ultrafiltration capacity (UFC), leading consequently to the technique malfunction. β-blockers have been considered deleterious for PM due to their association with loss of UFC and induction of fibrosis. Herein we analyzed the effects of Nebivolol, a new generation of β1-blocker, on PM alterations induced by PD fluids (PDF).

In vitro: We found that mesothelial cells (MCs) express β1-adrenergic receptor. MCs were treated with TGF-β to induce mesothelial-to-mesenchymal transition (MMT) and co-treated with Nebivolol. Nebivolol reversed the TGF-β effects, decreasing extracellular matrix synthesis, and improved the fibrinolytic capacity, decreasing plasminogen activator inhibitor-1 (PAI-1) and increasing tissue-type plasminogen activator (tPA) supernatant levels. Moreover, Nebivolol partially inhibited MMT and decreased vascular endothelial growth factor (VEGF) and IL-6 levels in supernatants.

In vivo: Twenty-one C57BL/6 mice were divided into 3 groups. Control group carried a catheter without PDF infusion. Study group received intraperitoneally PDF and oral Nebivolol during 30 days. PDF group received PDF alone. Nebivolol maintained the UFC and reduced PM thickness, MMT and angiogenesis promoted by PDF. It also improved the fibrinolytic capacity in PD effluents decreasing PAI-1 and IL-8 and increased tPA levels.

Conclusion: Nebivolol protects PM from PDF-induced damage, promoting anti-fibrotic, anti-angiogenic, anti-inflammatory and pro-fibrinolytic effects.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 8780