What question did this study set out to answer?

This research aims to determine if plasma-derived small extracellular vesicle miR-660-5p can predict carotid plaque vulnerability and postoperative cardiovascular risks.

March 26, 2026Open Access

Plasma-derived small extracellular vesicle miR-660-5p as a predictor for carotid plaque vulnerability and postoperative major adverse cardiovascular event risk

Key Result

Elevated plasma-derived sEV miR-660-5p independently predicts carotid plaque vulnerability and a higher risk of 3-year major adverse cardiovascular events following endarterectomy.

Key Points

This research aims to determine if plasma-derived small extracellular vesicle miR-660-5p can predict carotid plaque vulnerability and postoperative cardiovascular risks.
Enrolled carotid atherosclerotic stenosis patients in four cohorts including sequencing and validation cohorts.
Utilized high-throughput nano-bio chip integrated system for quantification of candidate miRNAs in plasma-derived sEVs.
Analyzed the association of miR-660-5p levels with vulnerability and major adverse cardiovascular events over three years.
Significant upregulation of miR-660-5p was found in vulnerable plaque-derived sEVs.
miR-660-5p levels correlated positively between matched plaque- and plasma-derived sEVs from individual patients.
Elevated miR-660-5p levels were independently associated with increased risk of major adverse cardiovascular events after endarterectomy.

Structured PICO

Does plasma-derived sEV miR-660-5p predict carotid plaque vulnerability and 3-year MACE risk in patients with carotid atherosclerotic stenosis?

Population

580 patients with carotid atherosclerotic stenosis (CAS) retrospectively enrolled into four cohorts: sequencing (n=12), discovery (n=62), validation 1 (endarterectomy cases, n=180), and validation 2 (stenting cases, n=326).

Intervention

Measurement of plasma-derived small extracellular vesicle (sEV) miR-660-5p levels

Outcome

Carotid plaque vulnerability (defined by histopathological criteria or Plaque-RADS criteria) and 3-year post-endarterectomy major adverse cardiovascular events (MACE)surrogate

Plasma-derived sEV miR-660-5p is a promising non-invasive biomarker for assessing carotid plaque vulnerability and predicting 3-year MACE risk after carotid endarterectomy.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Building on our previous isolation of plaque-derived small extracellular vesicles (sEVs) from carotid atherosclerotic stenosis (CAS) patients, this study aimed to identify plasma sEV-encapsulated miRNAs that reflect plaque vulnerability and predict clinical outcomes, based on differentially expressed miRNAs identified in sEVs from stable versus vulnerable plaques. CAS patients were retrospectively enrolled into four complementary cohorts: (1) a sequencing cohort (n=12) for miRNA profiling of plaque-derived sEVs; (2) a discovery cohort (n=62) to identify candidate plasma-derived sEV miRNAs associated with plaque vulnerability; and (3) validation cohort 1 (n=180; endarterectomy cases) and (4) validation cohort 2 (n=326; stenting cases) for validating the diagnostic efficacy of the identified plasma-derived sEV miRNAs. Candidate miRNAs were quantified using a High-throughput nano-bio chip integrated system (HNCIB). Their associations with plaque vulnerability and 3-year post-endarterectomy major adverse cardiovascular events (MACE) were analyzed. MiRNA sequencing revealed significant upregulation of miR-660-5p in vulnerable plaque-derived sEVs. Its expression levels showed a significant positive correlation between matched plaque- and plasma-derived sEVs from the same patient. Moreover, plasma-derived sEV miR-660-5p levels were independently associated with carotid plaque vulnerability in both validation cohorts, defined either by histopathological criteria (endarterectomy cases) or the clinically validated Plaque-Reporting and Data System (RADS) criteria (stenting cases). Additionally, elevated plasma-derived sEV miR-660-5p levels were also associated with a higher risk of 3-year post-endarterectomy MACE. Plasma-derived sEV miR-660-5p represents a promising non-invasive biomarker for assessing carotid plaque vulnerability and predicting 3-year MACE risk following carotid endarterectomy, offering potential for improved risk stratification and therapeutic targeting. • Plasma-derived sEV miR-660-5p served as an independent predictor of carotid plaque vulnerability. • Plasma-derived sEV miR-660-5p was associated with a higher risk of 3-year major adverse cardiovascular events following endarterectomy.