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Publications

Journal Article Ahead of print

PubMed: 42246983 DOI: 10.1093/eurheartj/ehag404

Extracellular vesicles in atherosclerotic cardiovascular disease: mechanisms and therapeutic implications.

Eur Heart J

Authors: Nicolas Amabile, Elena Aikawa, Françoise Dignat-George, Chantal M Boulanger, Yao Yao, Aurélie S Leroyer

Affiliations

  • Department of interventional Cardiology, Institut Cardiovasculaire Paris Sud, 6 avenue du Noyer Lambert, 91300 Massy, France.
  • Paris Cardiovascular Research Center, INSERM, Université Paris-Cité, 56 Rue Leblanc, 7 5015 Paris, France.
  • Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Center for Excellence in Vascular Biology, Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Centre de recherche en CardioVasculaire et Nutrition (C2VN), INSERM 1263, INRAE 1260, Aix Marseille University, Marseille, France.
  • Assistance Publique-Hôpitaux de Marseille, Biogenopole, CHU La Timone, APHM, Marseille, France.
  • Center for Healthy Aging Transdisciplinary Sciences, China Center for Health Development Studies, Peking University, Beijing, China. State Key Laboratory of Vascular Homeostasis and Remodelling, Peking University, Beijing, China. Key Laboratory of Epidemiology of Major Diseases, Peking University, Beijing, China.

Abstract

Extracellular vesicles (EVs) have emerged as central regulators of intercellular communication in cardiovascular pathology. In atherosclerosis, EVs derived from endothelial, leukocytes, platelets, erythrocytes, and vascular smooth muscle cells (VSMCs) actively participate in the initiation and progression of arterial wall inflammation. Endothelial-derived EVs can carry pro-inflammatory proteins and microRNAs that impair endothelial function, promote leukocyte adhesion, and enhance oxidative stress, thereby facilitating early lesion formation. Platelet- and leukocyte-derived EVs further amplify these processes by stimulating monocyte recruitment, cytokine release, and thrombotic signalling within the developing plaque. As atherosclerotic lesions mature, EVs contribute to key cellular phenotypes, including macrophage foam cell formation and VSMC switching towards synthetic or osteogenic states. These vesicles transport bioactive lipids, enzymes, and nucleic acids that influence cholesterol handling, extracellular matrix remodelling, and apoptotic signalling, ultimately contributing to plaque instability. EVs are also critical drivers of vascular calcification, a hallmark of advanced atherosclerosis. VSMC- and macrophage-derived EVs can serve as nucleation sites for hydroxyapatite deposition, particularly when enriched with phosphatidylserine, annexins, or calcification-regulatory microRNAs. Dysregulated mineral metabolism, oxidative stress, and inflammation further modify EV cargo in ways that favour calcifying microenvironments. As these microcalcifications coalesce, they increase arterial stiffness but also contribute to plaque instability. Given their accessibility in circulation and their mechanistic involvement, EVs offer promising opportunities as biomarkers for monitoring atherosclerosis development, as well as therapeutic targets. Modulating EV release, modifying their composition, or engineering EV-based delivery systems represents an innovative frontier for future therapeutic strategies in atherosclerotic disease.

MeSH

Cells, Extracellular Vesicles, Macrophages, Stress, Physiological, Cardiovascular Diseases, Oxidative Stress, Cardiology, Leukocytes, Atherosclerosis, Therapeutics, Blood Platelets