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TRANSLATIONAL PHYSIOLOGY

Characterization of blood borne microparticles as markers of premature coronary calcification in newly menopausal women

Departments of ¹Surgery and Physiology and Biomedical Engineering, ²Biochemistry and Molecular Biology and Hematology, ³Internal Medicine, Divisions of Hematology, ⁴Cardiovascular Diseases, and ⁵Radiology, Mayo Clinic College of Medicine, Rochester, Minnesota; ⁶Los Angeles Biomedical Research Institute at Harbor University of California at Los Angeles, Torrance, California; and the ⁷Kronos Longevity Research Institute, Phoenix, Arizona

Submitted 22 February 2008 ; accepted in final form 3 July 2008

While the risk for symptomatic atherosclerotic disease increases after menopause, currently recognized risk factors do not identify ongoing disease processes in low-risk women. This study tested the hypothesis that circulating cell-derived microparticles may reflect disease processes in women defined as low risk by the Framingham risk score. The concentration and phenotype of circulating microparticles were evaluated in a cross-sectional study of apparently healthy menopausal women, screened for enrollment into the Kronos Early Estrogen Prevention Study. Microparticles were evaluated by flow cytometry, and coronary artery calcification (CAC) was scored using 64-slice computed tomography scanners. The procoagulant activity of isolated microparticles was determined with a sensitive fluorescent thrombin generation assay. Chronological age, body mass index, serum lipids, systolic blood pressure (Framingham risk score < 10%, range 1–3%), and high-sensitivity C-reactive protein did not differ significantly among women with low (0 < 35; range, 0.3–32 Agatston units) or high (>50; range, 93–315 Agatston units) CAC compared with women without calcification. The total concentration and percentage of microparticles derived from platelets and endothelial cells were greatest in women with high CAC scores. The thrombin-generating capacity of the isolated microparticles correlated with phosphatidylserine expression, which also was greatest in women with high CAC scores. The percentages of microparticles expressing granulocyte and monocyte markers were not significantly different among groups. Therefore, the characterization of platelet and endothelial microparticles may identify early menopausal women with premature CAC who would not otherwise be identified by the usual risk factor analysis.

phosphatidylserine; procoagulant activity; thrombosis

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