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

Oncotarget. 2017 Feb 28;8(9):15553-15562. doi: 10.18632/oncotarget.14948.

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.

Keywords: albuminuria; endothelial dysfunction; extracellular vesicles; hypertension; proteomics.

MeSH terms

  • Aged
  • Albuminuria / blood
  • Albuminuria / metabolism*
  • Biomarkers / blood
  • Biomarkers / metabolism
  • DNA Helicases / metabolism*
  • DNA-Binding Proteins / metabolism*
  • E-Selectin / metabolism
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / physiopathology
  • Extracellular Vesicles / metabolism*
  • Extracellular Vesicles / ultrastructure
  • Female
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Humans
  • Hypertension / blood
  • Hypertension / metabolism*
  • Male
  • Microscopy, Confocal
  • Microscopy, Electron
  • Middle Aged
  • Protein Serine-Threonine Kinases / metabolism*
  • Proteomics / methods
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Biomarkers
  • DNA-Binding Proteins
  • E-Selectin
  • Guanine Nucleotide Exchange Factors
  • Tumor Necrosis Factor-alpha
  • KALRN protein, human
  • Protein Serine-Threonine Kinases
  • DNA Helicases
  • CHD7 protein, human