Characterization of blood borne microparticles as markers of premature coronary calcification in newly menopausal women
Characterization of blood borne microparticles as markers of premature coronary calcification in newly menopausal women
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DOI：
10.1152/ajpheart.00193.2008
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发表时间：
2008-09-01
影响因子：
4.8
通讯作者：
Miller, Virginia M.
中科院分区：
文献类型：
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作者：
Jayachandran, Muthuvel;Litwiller, Robert D.;Miller, Virginia M.
虽然绝经后症状性动脉粥样硬化疾病的风险增加，但目前公认的风险因素并不能确定低风险女性持续的疾病过程。这项研究检验了以下假设：循环细胞衍生的微粒可能反映了弗雷明汉风险评分定义为低风险的女性的疾病过程。在一项对表面健康的更年期妇女进行的横断面研究中评估了循环微粒的浓度和表型，这些妇女经过筛选参加了克罗诺斯早期雌激素预防研究。通过流式细胞术评估微粒，并使用 64 层计算机断层扫描仪对冠状动脉钙化 (CAC) 进行评分。用灵敏的荧光凝血酶生成测定法测定分离的微粒的促凝血活性。与无钙化的女性相比，低 CAC（0 < 35；范围，0.3-32 Agatson 单位）或高（> 50；范围，93-315 Agatston 单位）CAC 的女性的实足年龄、体重指数、血脂、收缩压（Framingham 风险评分 < 10%，范围 1-3%）和高敏 C 反应蛋白没有显着差异。在 CAC 评分高的女性中，源自血小板和内皮细胞的微粒的总浓度和百分比最高。分离出的微粒的凝血酶生成能力与磷脂酰丝氨酸的表达相关，磷脂酰丝氨酸的表达在 CAC 评分高的女性中也最强。表达粒细胞和单核细胞标记物的微粒的百分比在各组之间没有显着差异。因此，血小板和内皮微粒的特征可以识别患有过早 CAC 的早期绝经女性，而通常的危险因素分析无法识别出这些女性。
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.