Microvesicles from indoxyl sulfate-treated endothelial cells induce vascular calcification in vitro

• Published in: Computational and structural biotechnology journal 2020-01, Vol.18, p.953-966
• Main Authors: Alique, Matilde, Bodega, Guillermo, Corchete, Elena, García-Menéndez, Estefanya, de Sequera, Patricia, Luque, Rafael, Rodríguez-Padrón, Daily, Marqués, María, Portolés, José, Carracedo, Julia, Ramírez, Rafael
• Format: Article
• Language: English
• Subjects: Calcification; Endothelial cells; Microvesicles; Uremic toxins; Vascular cells
• ISSN: 2001-0370; 2001-0370
• DOI: 10.1016/j.csbj.2020.04.006

Microvesicles derived from indoxyl sulfate-treated endothelial cells induced vascular calcification in vitro. [Display omitted] •The identification of chronic kidney disease (CKD) at risk of vascular calcification development seems to be essential for preventing them from being at a significantly high risk of premature cardiovascular morbi-mortality.•It is necessary to gain further knowledge about the initial events that allow the progress of this pathology.•We report that indoxyl sulfate-damaged endothelial cells produce microvesicles that can trigger vascular calcification.•The number of endothelial calcified microvesicles in the plasma could be determined and used as a diagnostic tool to identify CKD patient risk. Vascular calcification (VC), an unpredictable pathophysiological process and critical event in patients with cardiovascular diseases (CVDs), is the leading cause of morbi-mortality and disability in chronic kidney disease (CKD) patients worldwide. Currently, no diagnostic method is available for identifying patients at risk of VC development; the pathology is detected when the process is irreversible. Extracellular vesicles (EVs) from endothelial cells might promote VC. Therefore, their evaluation and characterization could be useful for designing new diagnostic tools. The aim of the present study is to investigate whether microvesicles (MVs) from endothelial cells damaged by uremic toxin and indoxyl sulfate (IS) could induce calcification in human vascular smooth muscle cells (VMSCs). Besides, we have also analyzed the molecular mechanisms by which these endothelial MVs can promote VC development. Endothelial damage has been evaluated according to the percentage of senescence in endothelial cells, differential microRNAs in endothelial cells, and the amount of MVs released per cell. To identify the role of MVs in VC, VSMCs were treated with MVs from IS-treated endothelial cells. Calcium, inflammatory gene expression, and procalcification mediator levels in VSMCs were determined. IS-treated endothelial cells underwent senescence and exhibited modulated microRNA expression and an increase in the release of MVs. VSMCs exposed to these MVs modulated the expression of pro-inflammatory genes and some mediators involved in calcification progression. MVs produced by IS-treated endothelial cells promoted calcification in VSMCs.