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Role of endothelial microvesicles released by p-cresol on endothelial dysfunction
Fatima Guerrero1,2, Andres Carmona3, Teresa Obrero3
1Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Reina Sofia University Hospital, University of Cordoba, Córdoba, Spain. fatima.guerrero@imibic.org.
Scientific Reports
|July 2, 2020
Summary
Protein-bound uremic toxins like p-cresol accumulate in CKD, harming endothelial cells. P-cresol-induced microvesicles impair endothelial repair and promote senescence, potentially via specific microRNAs.
Area of Science:
- Nephrology
- Cardiovascular Biology
- Molecular Biology
Background:
- Protein-bound uremic toxins, such as p-cresol, are poorly cleared by dialysis and contribute to chronic kidney disease (CKD) and cardiovascular disease (CVD) progression.
- Uremic toxins induce pathological effects including inflammation, endothelial dysfunction, and the release of endothelial microvesicles.
- The specific role of p-cresol in the formation and function of endothelial microvesicles remains uninvestigated.
Purpose of the Study:
- To evaluate the effects of p-cresol-induced endothelial microvesicles (PcEMV) on endothelial dysfunction.
- To investigate the impact of PcEMV on the endothelial repair process in vitro.
- To identify potential microRNA (miRNA) involvement in p-cresol-mediated endothelial damage.
Main Methods:
- An in vitro model of endothelial damage was established using p-cresol.
- The functional effects of PcEMV on endothelial cell repair, migration, and vascular structure formation were assessed.
- Cellular senescence and the expression of miRNA-146b-5p and miRNA-223-3p were analyzed in treated endothelial cells.
Main Results:
- P-cresol significantly increased the release of microvesicles from endothelial cells.
- PcEMV impaired endothelial cell regenerative capacity, reducing migration and vascular structure formation.
- Treatment with PcEMV led to increased cellular senescence and deregulation of miRNA-146b-5p and miRNA-223-3p expression.
Conclusions:
- Microvesicles generated by p-cresol-treated endothelial cells (PcEMV) interfere with endothelial repair mechanisms.
- PcEMV decrease endothelial cell migration, impair new vessel formation, and increase cellular senescence.
- These detrimental effects may be mediated by the upregulation of specific miRNAs, namely miRNA-146b-5p and miRNA-223-3p.
