Annexin A1-dependent tethering promotes extracellular vesicle aggregation revealed with single-extracellular vesicle analysis

Maximillian A Rogers, Fabrizio Buffolo, Florian Schlotter, Samantha K Atkins, Lang H Lee, Arda Halu, Mark C Blaser, Elena Tsolaki, Hideyuki Higashi, Kristin Luther, George Daaboul, Carlijn V C Bouten, Simon C Body, Sasha A Singh, Sergio Bertazzo, Peter Libby, Masanori Aikawa, Elena Aikawa (Corresponding author)

Onderzoeksoutput: Bijdrage aan tijdschriftTijdschriftartikelAcademicpeer review

6 Citaten (Scopus)

Samenvatting

Extracellular vesicles (EVs) including plasma membrane-derived microvesicles and endosomal-derived exosomes aggregate by unknown mechanisms, forming microcalcifications that promote cardiovascular disease, the leading cause of death worldwide. Here, we show a framework for assessing cell-independent EV mechanisms in disease by suggesting that annexin A1 (ANXA1)-dependent tethering induces EV aggregation and microcalcification. We present single-EV microarray, a method to distinguish microvesicles from exosomes and assess heterogeneity at a single-EV level. Single-EV microarray and proteomics revealed increased ANXA1 primarily on aggregating and calcifying microvesicles. ANXA1 vesicle aggregation was suppressed by calcium chelation, altering pH, or ANXA1 neutralizing antibody. ANXA1 knockdown attenuated EV aggregation and microcalcification formation in human cardiovascular cells and acellular three-dimensional collagen hydrogels. Our findings explain why microcalcifications are more prone to form in vulnerable regions of plaque, regulating critical cardiovascular pathology, and likely extend to other EV-associated diseases, including autoimmune and neurodegenerative diseases and cancer.

Originele taal-2Engels
Artikelnummereabb1244
Aantal pagina's15
TijdschriftScience Advances
Volume6
Nummer van het tijdschrift38
DOI's
StatusGepubliceerd - 1 sep 2020

Bibliografische nota

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

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