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Updated: Jul 24, 2025
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Analysis of Extracellular Vesicle-Mediated Vascular Calcification Using In Vitro and In Vivo Models
Published on: January 27, 2023
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Multiomics of Tissue Extracellular Vesicles Identifies Unique Modulators of Atherosclerosis and Calcific Aortic Valve
Mark C Blaser1, Fabrizio Buffolo1, Arda Halu1,2
1Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine (M.C.B., F.B., A.H., M.E.T., F.S., H.H., C.L.C., L.A.S., S.K.A., M.A.R., T.P., S.A.S., M.A., E.A.).
Circulation
|July 10, 2023
Summary
Tissue-entrapped extracellular vesicles (EVs) play a role in cardiovascular calcification. This study reveals tissue-specific EV cargoes linked to calcific signaling pathways in arteries and valves, offering new insights into disease mechanisms.
Area of Science:
- Cardiovascular Biology
- Extracellular Vesicle Research
- Proteomics and Transcriptomics
Background:
- Aortic valve calcification and atherosclerosis often have different causes.
- Circulating extracellular vesicles (EVs) are cardiovascular disease biomarkers, but tissue-EV roles in mineralization are unknown.
Purpose of the Study:
- To investigate the cargoes, functions, and disease contributions of tissue-entrapped EVs in cardiovascular calcification.
- To compare proteomic and transcriptomic profiles of EVs from diseased carotid arteries and aortic valves.
Main Methods:
- Disease-stage proteomics on human carotid plaques and aortic valves.
- Isolation and vesiculomics (proteomics and small RNA-sequencing) of tissue-EVs.
- Network analyses and gene validation in primary cells.
Main Results:
- Proteomes of carotid plaques and aortic valves showed significant convergence but retained unique proteins.
- Disease progression altered EV protein and microRNA content, implicating shared pathways.
- Tissue-specific EV cargoes were linked to Notch and Wnt signaling, driving calcification.
Conclusions:
- This study is the first to compare proteomics of human carotid plaques and aortic valves, identifying distinct disease drivers.
- A novel vesiculomics strategy was developed to analyze EVs within fibrocalcific tissues.
- Tissue EVs play a significant role in modulating cardiovascular disease progression.
