Oncotarget

Research Papers:

Kalirin and CHD7: novel endothelial dysfunction indicators in circulating extracellular vesicles from hypertensive patients with albuminuria

Fernando de la Cuesta, Montserrat Baldan-Martin, Rafael Moreno-Luna, Gloria Alvarez-Llamas, Laura Gonzalez-Calero, Laura Mourino-Alvarez, Tamara Sastre-Oliva, Juan A. López, Jesús Vázquez, Gema Ruiz-Hurtado, Julian Segura, Fernando Vivanco, Luis M. Ruilope and Maria G. Barderas _

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Oncotarget. 2017; 8:15553-15562. https://doi.org/10.18632/oncotarget.14948

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Abstract

Fernando de la Cuesta1,6, Montserrat Baldan-Martin1, Rafael Moreno-Luna1, Gloria Alvarez-Llamas2, Laura Gonzalez-Calero2, Laura Mourino-Alvarez1, Tamara Sastre-Oliva1, Juan A. López3, Jesús Vázquez3, Gema Ruiz-Hurtado4, Julian Segura4, Fernando Vivanco2,5, Luis M. Ruilope4, Maria G. Barderas1

1Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos (HNP), SESCAM, Toledo, Spain

2Department of Immunology, IIS-Fundacion Jimenez Diaz, Madrid, Spain

3Unidad de Proteomica CNIC, Madrid, Spain

4Unidad de Hipertension, Instituto de Investigacion i + 12, Hospital Universitario 12 de Octubre, Madrid, Spain

5Departamento de Bioquimica y Biologia Molecular I, Universidad Complutense, Madrid, Spain

6Current address: Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, UK

Correspondence to:

Maria G. Barderas, email: [email protected]

Luis M. Ruilope, email: [email protected]

Keywords: extracellular vesicles, proteomics, endothelial dysfunction, hypertension, albuminuria

Received: August 17, 2016     Accepted: December 05, 2016     Published: February 01, 2017

ABSTRACT

Despite of the great advances in anti-hypertensive therapies, many patients under Renin-Angiotensin- System (RAS) suppression develop albuminuria, which is a clear indicator of therapeutic inefficiency. Hence, indicators of vascular function are needed to assess patients’ condition and help deciding future therapies.

Proteomic analysis of circulating extracellular vesicles (EVs) showed two proteins, kalirin and chromodomain-helicase-DNA-binding protein 7 (CHD7), increased in albuminuric patients. A positive correlation of both with the expression of the endothelial activation marker E-selectin was found in EVs. In vitro analysis using TNFα-treated adult human endothelial cells proved their involvement in endothelial cell activation.

Hence, we propose protein levels of kalirin and CHD7 in circulating EVs as novel endothelial dysfunction markers to monitor vascular condition in hypertensive patients with albuminuria.


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