title: Specific cell-derived microvesicles: Linking endothelial function to carotid artery intima-media thickness in low cardiovascular risk menopausal women.
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.
authors.affiliation: Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA; Department of Physiology & Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: miller.virginia@mayo.edu.
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Miller
authors.affiliation: Department of Health Sciences Research (Division of Biomedical Statistics and Informatics), Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Lahr
authors.affiliation: Department of Health Sciences Research (Division of Biomedical Statistics and Informatics), Mayo Clinic, Rochester, MN 55905, USA; Department of Health Sciences Research (Division of Epidemiology), Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Kent R
authors.initials: KR
authors.lastname: Bailey
authors.affiliation: Atherosclerosis Research Unit, University of Southern California, Los Angeles, CA 9033, USA.
authors.forename: Howard N
authors.initials: HN
authors.lastname: Hodis
authors.affiliation: Department of Internal Medicine (Division of Cardiovascular Diseases), Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Mulvagh
authors.affiliation: Department of Physiology & Biomedical Engineering, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Muthuvel
authors.initials: M
authors.lastname: Jayachandran
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism*; D002339:Carotid Arteries / Q000000981:diagnostic imaging*; D002340:Carotid Artery Diseases / Q000097:blood* / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology; D059168:Carotid Intima-Media Thickness; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D018450:Disease Progression; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D018836:Inflammation Mediators / Q000097:blood; D008137:Longitudinal Studies; D008365:Manometry; D008593:Menopause / Q000097:blood*; D008875:Middle Aged; D015539:Platelet Activation; D011237:Predictive Value of Tests; D025341:Principal Component Analysis; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators
keywords: Atherosclerosis; Inflammation; KEEPS; Kronos Early Estrogen Prevention Study; Leukocytes; Microparticles; Platelets