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

Abstract

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.

Circulating microvesicles in B-cell chronic lymphocytic leukemia can stimulate marrow stromal cells: implications for disease progression

“…Flow cytometric analyses demonstrated that the majority of MVs isolated from CLL plasma were positive for annexin V binding (typically, Ͼ90%; Figure 1A), and sizes were within 1.0 m, typical characteristics of MVs, 2 on the basis of forward/side scatter with the use of 1.0-m standard beads. 13 These were heterogeneous, membrane-encapsulated small vesicles ranging in size from 0.1 to 1.0 m as revealed under electron microscopy ( Figure 1B), also typical features of MV. Although significantly greater levels (P Ͻ .006) of MVs were demonstrable in the majority of CLL plasma ( Figure 1C), we could not find a significant association of MV levels with disease stage or other prognostic factors (data not shown).…”

Circulating platelet-derived microparticles are elevated in women with polycystic ovary syndrome diagnosed with the 1990 criteria and correlate with serum testosterone levels

“…Several lines of evidence suggest that PMPs contribute to the pathogenesis of atherothrombosis. Indeed, plasma PMPs are elevated in patients with established cardiovascular disease compared with healthy controls (18,19) and are positively correlated with the atherosclerotic burden (20). More importantly, preliminary results suggest that higher PMPs are associated with higher risk for cardiovascular events (18).…”

Thrombogenic microvesicles and white matter hyperintensities in postmenopausal women

“…Each KEEPS participant underwent a medical examination, including body morphometrics (BMI, waist/hip ratio measurements), an MRI scan, standard blood chemistries, highresolution B-mode ultrasound for the assessment of CIMT and CT for the assessment of CAC. 21,22 All CAC and CIMT results were read centrally by individuals blinded to participant demographics. 22 None of the women in the Mayo Clinic KEEPS-MRI study developed a neurologic or psychiatric disorder such as stroke or depression throughout the duration of the study.…”

“…24 Expression of activated platelet membrane glycoprotein IIb/IIIa complex binding to PAC-1 antibody (an indirect measure of the fibrinogen receptor complex) was measured by flow cytometry. 17,21,24 Blood-borne microvesicles. Numbers of activated plateletderived microvesicles and total numbers of thrombogenic (phosphatidylserine-positive defined by annexin V binding) microvesicles were obtained at baseline using binding of fluorophoreconjugated, platelet-specific CD42a antibody and recombinant annexin V, respectively, by flow cytometry.…”