title: Alterations in platelet function and cell-derived microvesicles in recently menopausal women: relationship to metabolic syndrome and atherogenic risk.
abstract: A woman's risk for metabolic syndrome (MS) increases at menopause, with an associated increase in risk for cardiovascular disease. We hypothesized that early menopause-related changes in platelet activity and concentrations of microvesicles derived from activated blood and vascular cells provide a mechanistic link to the early atherothrombotic process. Thus, platelet functions and cellular origin of blood-borne microvesicles in recently menopausal women (n = 118) enrolled in the Kronos Early Estrogen Prevention Study were correlated with components of MS and noninvasive measures of cardiovascular disease [carotid artery intima medial thickness (CIMT), coronary artery calcium (CAC) score, and endothelial reactive hyperemic index (RHI)]. Specific to individual components of the MS pentad, platelet number increased with increasing waist circumference, and platelet secretion of ATP and expression of P-selectin decreased with increasing blood glucose (p = 0.005) and blood pressure (p < 0.05), respectively. Waist circumference and systolic blood pressure were independently associated with monocyte- and endothelium-derived microvesicles (p < 0.05). Platelet-derived and total procoagulant phosphatidylserine-positive microvesicles, and systolic blood pressure correlated with CIMT (p < 0.05), but not with CAC or RHI. In summary, among recently menopausal women, specific platelet functions and concentrations of circulating activated cell membrane-derived procoagulant microvesicles change with individual components of MS. These cellular changes may explain in part how menopause contributes to MS and, eventually, to cardiovascular disease.
authors.affiliation: Department of Physiology & Biomedical Engineering, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA.
authors.forename: Muthuvel
authors.initials: M
authors.lastname: Jayachandran
authors.forename: Robert D
authors.initials: RD
authors.lastname: Litwiller
authors.forename: Brian D
authors.initials: BD
authors.lastname: Lahr
authors.forename: Kent R
authors.initials: KR
authors.lastname: Bailey
authors.forename: Whyte G
authors.initials: WG
authors.lastname: Owen
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Mulvagh
authors.forename: John A
authors.initials: JA
authors.lastname: Heit
authors.forename: Howard N
authors.initials: HN
authors.lastname: Hodis
authors.forename: S Mitchell
authors.initials: SM
authors.lastname: Harman
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Miller
mesh_terms: D000255:Adenosine Triphosphate / Q000097:blood; D000328:Adult; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D001792:Blood Platelets / Q000378:metabolism*; D001794:Blood Pressure; D002118:Calcium / Q000378:metabolism; D002339:Carotid Arteries / Q000473:pathology; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D003331:Coronary Vessels / Q000378:metabolism; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000503:physiopathology; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D008593:Menopause / Q000097:blood*; D024821:Metabolic Syndrome / Q000097:blood / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D008875:Middle Aged; D015999:Multivariate Analysis; D019007:P-Selectin / Q000097:blood; D010979:Platelet Function Tests; D012044:Regression Analysis; D018570:Risk Assessment; D012307:Risk Factors; D055105:Waist Circumference
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D019007:P-Selectin; C546937:SELP protein, human; D000255:Adenosine Triphosphate; D002118:Calcium