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Updated: Dec 22, 2025
Analysis of Extracellular Vesicle-Mediated Vascular Calcification Using In Vitro and In Vivo Models
Published on: January 27, 2023
Microvesicles from indoxyl sulfate-treated endothelial cells induce vascular calcification in vitro
Matilde Alique1, Guillermo Bodega2, Elena Corchete3
1Departamento de Biología de Sistemas, Universidad de Alcalá (IRYCIS), Alcalá de Henares, Madrid, Spain.
Insights
Microvesicles from damaged endothelial cells, exposed to uremic toxins, promote vascular calcification (VC) in smooth muscle cells. This finding could lead to new diagnostic tools for identifying VC risk in chronic kidney disease patients.
Area of Science:
- Cardiovascular Biology
- Nephrology
- Cell Biology
Background:
- Vascular calcification (VC) is a major cause of death in chronic kidney disease (CKD) patients.
- Current diagnostic methods cannot predict VC risk, as it's often detected late.
- Endothelial cells and their extracellular vesicles (EVs) may play a role in VC development.
Purpose of the Study:
- To investigate if microvesicles (MVs) from endothelial cells damaged by indoxyl sulfate (IS) induce calcification in vascular smooth muscle cells (VMSCs).
- To analyze the molecular mechanisms underlying IS-induced endothelial MVs' role in promoting VC.
Main Methods:
- Endothelial cells were damaged using IS, and damage was assessed by senescence, microRNA changes, and MV release.
- Vascular smooth muscle cells (VMSCs) were treated with MVs from IS-damaged endothelial cells.
- Calcium levels, inflammatory gene expression, and procalcification mediators in VMSCs were measured.
Main Results:
- IS-treated endothelial cells showed increased senescence, altered microRNA expression, and higher MV release.
- MVs from IS-treated endothelial cells induced modulated expression of inflammatory genes and calcification mediators in VMSCs.
- Exposure to these MVs promoted calcification in VMSCs.
Conclusions:
- Microvesicles derived from IS-damaged endothelial cells can induce vascular calcification in VMSCs.
- These findings suggest endothelial MVs as potential biomarkers for predicting VC risk.
- Further research into endothelial MVs may offer new diagnostic strategies for VC in CKD.
Abstract:
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.
