Liquid Biopsy of Extracellular Microvesicles Maps Coronary Calcification and Atherosclerotic Plaque in Asymptomatic Patients With Familial Hypercholesterolemia A Computed Tomographic Angiography Imaging Study
Liquid Biopsy of Extracellular Microvesicles Maps Coronary Calcification and Atherosclerotic Plaque in Asymptomatic Patients With Familial Hypercholesterolemia A Computed Tomographic Angiography Imaging Study
复制标题
DOI：
10.1161/atvbaha.118.312414
复制
发表时间：
2019-05-01
影响因子：
8.7
通讯作者：
Badimon, Lina
中科院分区：
文献类型：
--
作者：
Chiva-Blanch, Gemma;Padro, Teresa;Badimon, Lina
杂合子家族性高胆固醇血症（FH）是最常见的与早发性动脉粥样硬化性心血管疾病相关的遗传性疾病。当细胞被激活时，循环微泡（cMV）被释放。我们调查了cMV是否可以提供信息冠状动脉钙化和动脉粥样硬化在FH patient.Approach和Results-Eighty-Two患者（平均44 +/- 9岁）的分子诊断杂合子FH和无症状的心血管疾病进行了调查。通过计算机断层扫描血管造影进行动脉粥样硬化斑块表征，并计算Agatston冠状动脉钙化评分和斑块组成总和。使用AV（膜联蛋白V）和细胞表面特异性抗体通过流式细胞术定量cMV。82例FH患者中，48例出现动脉粥样硬化斑块。动脉粥样硬化患者为男性，年龄较大，其比例高于无动脉粥样硬化斑块的患者。与无动脉粥样硬化斑块的FH患者相比，有动脉粥样硬化斑块的FH患者显示出更高水平的总AV+ cMV、血小板来源的cMV AV+、粒细胞和中性粒细胞来源的cMV AV+以及内皮细胞来源的cMV AV（+/-）。斑块成分总和与血小板和内皮源性cMV相关，Agatston冠状动脉钙评分与粒细胞、血小板和内皮源性cMV相关。受试者工作特征曲线分析表明，血小板、粒细胞、中性粒细胞和内皮源性cMV的聚集在一起，增加了对斑块存在的特定SAFEHEART（西班牙家族性高胆固醇血症队列研究）风险方程的显著预测值（曲线下面积= 0.866，95%CI，0.775-0.958; P
Objective-Heterozygous familial hypercholesterolemia (FH) is the most common genetic disorder associated with premature atherosclerotic cardiovascular disease. Circulating microvesicles (cMV) are released when cells are activated. We investigated whether cMV could provide information on coronary calcification and atherosclerosis in FH patients.Approach and Results-Eighty-two patients (mean of 44 +/- 9 years old) with molecular diagnosis of heterozygous FH and asymptomatic cardiovascular disease were investigated. Atherosclerotic plaque characterization was performed by computed tomography angiography, and Agatston coronary calcium score and plaque composition sum were calculated. cMV were quantified by flow cytometry using AV (annexin V) and cell surface-specific antibodies. Of the 82 FH patients, 48 presented atherosclerotic plaque. Patients with atherosclerosis were men and older in a higher percentage than patients without atherosclerotic plaque. FH patients with atherosclerotic plaque showed higher levels of total AV+ cMV, cMV AV+ from platelet origin, from granulocytes and neutrophils, and cMV AV(+/-) from endothelial cells than FH-patients without atherosclerotic plaque. Plaque composition sum correlated with platelet-and endothelial-derived cMV, and Agatston coronary calcium score correlated with granulocyte-, platelet-, and endothelial-derived cMV. Receiver operating characteristic curve analyses indicated that the cluster of platelet-, granulocyte-, neutrophil, and endothelial-derived cMV considered together, added significant predictive value to the specific SAFEHEART (Spanish Familial Hypercholesterolaemia Cohort Study) risk equation for plaque presence (area under the curve= 0.866, 95% CI, 0.775-0.958; P