Specific cell-derived microvesicles: Linking endothelial function to carotid artery intima-media thickness in low cardiovascular risk menopausal women

Virginia M Miller, Brian D. Lahr, Kent R Bailey, Howard N. Hodis, Sharon L. Mulvagh, Muthuvel Jayachandran

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)21-28
Number of pages8
JournalAtherosclerosis
Volume246
DOIs
StatePublished - Mar 1 2016

Fingerprint

Carotid Intima-Media Thickness
Carotid Arteries
Platelet Activation
Principal Component Analysis
Coagulants
Vascular Cell Adhesion Molecule-1
Blood Cells
Fibrinogen Receptors
Tissue Adhesions
CD45 Antigens
P-Selectin
Manometry
Vascular Endothelium
Cell Adhesion Molecules
Thromboplastin
Intercellular Adhesion Molecule-1
Cell Adhesion
Blood Vessels
Pulse
Monocytes

Keywords

  • Atherosclerosis
  • Inflammation
  • KEEPS
  • Kronos Early Estrogen Prevention Study
  • Leukocytes
  • Microparticles
  • Platelets

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Specific cell-derived microvesicles : Linking endothelial function to carotid artery intima-media thickness in low cardiovascular risk menopausal women. / Miller, Virginia M; Lahr, Brian D.; Bailey, Kent R; Hodis, Howard N.; Mulvagh, Sharon L.; Jayachandran, Muthuvel.

In: Atherosclerosis, Vol. 246, 01.03.2016, p. 21-28.

Research output: Contribution to journalArticle

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abstract = "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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AU - Miller, Virginia M

AU - Lahr, Brian D.

AU - Bailey, Kent R

AU - Hodis, Howard N.

AU - Mulvagh, Sharon L.

AU - Jayachandran, Muthuvel

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N2 - 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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KW - Microparticles

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