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

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.

Importance of extracellular vesicles in hypertension

“…Subsequent studies aim to analyze the whole spectrum of EVs, including the functional biomolecules within EVs. Proteomic analysis of circulating EVs in albuminuric hypertensive patients showed that two proteins, kalirin and chromodomain-helicase-DNA-binding protein 7, increased with RAS suppression 120. Because expression of these proteins in circulating EVs positively correlates with the endothelial activation marker E-selectin, it is used to monitor the vascular condition of these patients.…”

Application of Extracellular Vesicles Proteomics to Cardiovascular Disease: Guidelines, Data Analysis, and Future Perspectives

“…Circulating levels of EVs have been found to be increased in hypertension . De la cuesta et al . performed a proteomic analysis comparing EVs from hypertensive patients with or without albuminuria.…”

Rapid, Automated, and Specific Immunoassay to Directly Measure Matrix Metalloproteinase-9–Tissue Inhibitor of Metalloproteinase-1 Interactions in Human Plasma Using AlphaLISA Technology: A New Alternative to Classical ELISA

“…Representative data from MMP-9–TIMP-1 AlphaLISA ® interactions in human plasma samples are shown in a study recently published by our laboratory ( 16 ). Similar to that study, here we analyzed MMP-9–TIMP-1 immunocomplexes in plasma samples from hypertensive patients with or without albuminuria as an indicator of endothelial dysfunction and arterial stiffness ( 22 – 25 ). We found that plasma from patients with albuminuria had significantly less MMP-9–TIMP-1 complexes than equivalent samples from non-albuminuric patients (Figure 5 A; P < 0.01).…”