Review of extracellular vesicles in vascular calcification and cardiovascular disease

Photo by National Institute of Allergy and Infectious Diseases / Unsplash

Frontiers in Medicine Published May 7, 2026 Medically reviewed May 7, 2026 DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider extracellular vesicles as promising biomarkers and therapeutic targets for vascular calcification.

This narrative review focuses on the role of extracellular vesicles in vascular calcification and cardiovascular disease. The scope includes the dual nature of these vesicles, which can act as pro-calcific agents or anti-calcific agents depending on the balance of signaling molecules involved. The authors describe how extracellular vesicles drive phenotypic transformation and serve as nucleation cores while also maintaining vascular homeostasis.

The review synthesizes arguments regarding the potential of extracellular vesicles as new biomarkers, therapeutic intervention targets, and drug delivery carriers. The authors emphasize that the progress of vascular calcification depends on the balance between pro-calcific and anti-calcific extracellular vesicles. This balance determines whether the vesicles antagonize osteogenic signaling pathways or deliver pro-inflammatory and osteogenic signaling molecules.

The authors note significant limitations, including the exploratory nature of current diagnostic and therapeutic strategies and the highlighting of current knowledge gaps. No specific adverse events, sample sizes, or follow-up durations are reported. The practice relevance is that extracellular vesicles have become a highly promising source of new biomarkers and therapeutic intervention targets, though further research is needed.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedMay 2026

View Original Abstract ↓

Vascular calcification (VC) is an active and regulated pathological process, which plays a central role in cardiovascular disease. Extracellular vesicles (EVs) are now recognized as crucial players in this pathology. EVs are nanoscale membrane vesicles secreted by cells. According to their biogenesis, they are mainly divided into exosomes, microvesicles and apoptotic bodies. They are rich in proteins, nucleic acids, lipids and other biologically active molecules. EVs play a dual role in VC. Regarding the pro-calcific role, EVs released by vascular smooth muscle cells (VSMCs), endothelial cells (ECs), and macrophages drive the phenotypic transformation of VSMCs by serving as nucleation cores for hydroxyapatite crystal deposition and by delivering pro-inflammatory and osteogenic signaling molecules. In addition to local effects, EVs also mediate long-distance intercellular communication. Together, these actions establish and amplify a pro-calcific microenvironment. In the aspect of anti-calcification, protective EVs can antagonize the osteogenic signaling pathway and maintain vascular homeostasis by delivering inhibitory microRNA (miRNA) (such as miR-126-5p, miR-133) and proteins (such as matrix Gla protein). The progress of VC depends on the balance between pro-calcific and anti-calcific EVs. Given their central position in pathology, EVs have become a highly promising source of new biomarkers, therapeutic intervention targets and drug delivery carriers. This review systematically summarizes the basic biological characteristics of EVs and the specific mechanisms underlying their dual regulatory roles in VC. It also discusses the challenges and future prospects for their clinical translation, thereby highlighting current knowledge gaps and outlining the exploratory nature of diagnostic and therapeutic strategies against VC.