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Specific cell-derived microvesicles: Linking endothelial function to carotid artery intima-media thickness in low
Virginia M Miller1, Brian D Lahr2, Kent R Bailey3
1Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA; Department of Physiology & Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.
Insights
Microvesicles (MV) from activated cells and those expressing adhesion molecules correlate with early vascular changes in menopausal women. Platelet activation markers are linked to changes in endothelial function, suggesting potential cardiovascular risk indicators.
Area of Science:
- Cardiovascular disease research
- Menopause and vascular health
- Biomarker discovery
Background:
- Endothelial dysfunction (measured by reactive hyperemic index, RHI) and increased carotid intima-media thickness (CIMT) are observed in recently menopausal women.
- The underlying factors connecting RHI and CIMT in low-risk menopausal women remain unclear.
Purpose of the Study:
- To longitudinally assess markers of platelet activation and cell-derived microvesicles (MV) in relation to RHI and CIMT.
- To investigate these associations in asymptomatic, low-risk menopausal women.
Main Methods:
- Evaluated RHI (n=93) and CIMT (n=113) in women from the Kronos Early Estrogen Prevention Study (KEEPS).
- Measured platelet activation markers and specific cell-derived, blood-borne microvesicles (MV) longitudinally.
- Utilized digital pulse tonometry for RHI and ultrasound for CIMT.
Main Results:
- Carotid intima-media thickness (CIMT) significantly increased over 4 years, while RHI did not.
- Increased CIMT correlated with higher levels of microvesicles (MV) positive for leukocyte antigen (CD45) and VCAM-1.
- Principal component analysis revealed associations between MV expressing markers of vascular endothelium, inflammatory cells, pro-coagulant factors, and cell adhesion molecules with changes in RHI and CIMT. Platelet activation markers were linked to RHI changes.
Conclusions:
- Microvesicles (MV) from activated endothelial and inflammatory cells, expressing adhesion and pro-coagulant molecules, may indicate early vascular dysfunction in low-risk menopausal women.
- Further development of microvesicle (MV) assays is needed as non-conventional tools for assessing cardiovascular risk in asymptomatic women.
Background:
Decreases in endothelial function measured by reactive hyperemic index (RHI) correlated with increases in carotid intima-media thickness (CIMT) in recently menopausal women with a low risk cardiovascular profile. Factors linking this association are unknown.
Objective:
Assess, longitudinally, markers of platelet activation and cell-derived, blood-borne microvesicles (MV) in relationship to RHI and CIMT in asymptomatic, low risk menopausal women.
Methods:
RHI by digital pulse tonometry (n = 93), CIMT by ultrasound (n = 113), measures of platelet activation and specific cell-derived, blood-borne MV were evaluated in women throughout the Kronos Early Estrogen Prevention Study (KEEPS) at Mayo Clinic.
Results:
CIMT, but not RHI, increased significantly over 4 years. The average change in CIMT correlated significantly with the average follow-up values of MV positive for common leukocyte antigen [CD45; ρ = 0.285 (P = 0.002)] and VCAM-1 [ρ = 0.270 (P = 0.0040)]. Using principal components analysis (PC) on the aggregate set of average follow-up measures, the first derived PC representing numbers of MV positive for markers of vascular endothelium, inflammatory cells (leukocyte and monocytes), pro-coagulant (tissue factor), and cell adhesion molecules (ICAM-1 and VCAM-1) associated with changes in RHI and CIMT. Changes in RHI associated with another PC defined by measures of platelet activation (dense granular ATP secretion, surface expression of P-selectin and fibrinogen receptors).
Conclusions:
MV derived from activated endothelial and inflammatory cells, and those expressing cell adhesion and pro-coagulant molecules may reflect early vascular dysfunction in low risk menopausal women. Assays of MV as non-conventional measures to assess cardiovascular risk in asymptomatic women remain to be developed.
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