Kalirin and CHD7: novel endothelial dysfunction indicators in circulating extracellular vesicles from hypertensive patients with albuminuria.
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.
Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos (HNP), SESCAM, Toledo, Spain.|Current address: Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
Fernando
F
de la Cuesta
Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos (HNP), SESCAM, Toledo, Spain.
Montserrat
M
Baldan-Martin
Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos (HNP), SESCAM, Toledo, Spain.
Rafael
R
Moreno-Luna
Department of Immunology, IIS-Fundacion Jimenez Diaz, Madrid, Spain.
Gloria
G
Alvarez-Llamas
Department of Immunology, IIS-Fundacion Jimenez Diaz, Madrid, Spain.
Laura
L
Gonzalez-Calero
Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos (HNP), SESCAM, Toledo, Spain.
Laura
L
Mourino-Alvarez
Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos (HNP), SESCAM, Toledo, Spain.
Tamara
T
Sastre-Oliva
Unidad de Proteomica CNIC, Madrid, Spain.
Juan A
JA
López
Unidad de Proteomica CNIC, Madrid, Spain.
Jesús
J
Vázquez
Unidad de Hipertension, Instituto de Investigacion i + 12, Hospital Universitario 12 de Octubre, Madrid, Spain.
Gema
G
Ruiz-Hurtado
Unidad de Hipertension, Instituto de Investigacion i + 12, Hospital Universitario 12 de Octubre, Madrid, Spain.
Julian
J
Segura
Department of Immunology, IIS-Fundacion Jimenez Diaz, Madrid, Spain.|Departamento de Bioquimica y Biologia Molecular I, Universidad Complutense, Madrid, Spain.
Fernando
F
Vivanco
Unidad de Hipertension, Instituto de Investigacion i + 12, Hospital Universitario 12 de Octubre, Madrid, Spain.
Luis M
LM
Ruilope
Department of Vascular Physiopathology, Hospital Nacional de Paraplejicos (HNP), SESCAM, Toledo, Spain.
Maria G
MG
Barderas
D000368:Aged; D000419:Albuminuria / Q000097:blood / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D004265:DNA Helicases / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000067128:Extracellular Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D015415:Biomarkers; D004268:DNA-Binding Proteins; D019040:E-Selectin; D020662:Guanine Nucleotide Exchange Factors; D014409:Tumor Necrosis Factor-alpha; C503866:KALRN protein, human; D017346:Protein Serine-Threonine Kinases; D004265:DNA Helicases; C491434:CHD7 protein, human
albuminuria; endothelial dysfunction; extracellular vesicles; hypertension; proteomics