Serum extracellular vesicle protein levels are associated with acute coronary syndrome
Serum extracellular vesicle protein levels are associated with acute coronary syndrome
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DOI：
10.1177/2048872612471212
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发表时间：
2013-03-01
影响因子：
4.1
通讯作者：
Mosterd, Arend
中科院分区：
文献类型：
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作者：
de Hoog, Vince C.;Timmers, Leo;Mosterd, Arend
目的：生物标志物在急性冠脉综合征（ACS）的早期检测中是必不可少的。血清细胞外囊泡是血浆中含有蛋白质和RNA的小囊泡，已被证明参与acs相关的过程，如凋亡和凝血。因此，我们假设血清细胞外囊泡蛋白水平与ACS有关。方法和结果：用差异q -蛋白质组学鉴定了三种可能与ACS相关的血清细胞外囊泡蛋白，并对就诊于急诊科的471例疑似ACS患者（其中30%患有ACS）的冷冻血清样本进行了评估。使用ExoQuick分离囊泡后测定蛋白水平。比较ACS与非ACS患者不同蛋白的平均血清胞外囊泡浓度。选择的蛋白质在单变量逻辑回归模型中进行测试，以及在多变量模型中调整心血管危险因素。对男性和女性进行了单独的分析。在多因素logistic回归分析中，多基因免疫球蛋白受体（pIgR, OR 1.630, p=0.026）、胱抑素C （OR 1.641, p=0.021）、补体因子C5a （C5a, OR 1.495, p=0.025）与ACS显著相关，而总囊泡蛋白浓度具有临界显著性。个体蛋白与ACS的相关性在男性中明显更强。结论：这些数据表明血清细胞外囊泡pIgR、胱抑素C和C5a浓度与ACS独立相关，且存在显著的性别差异。这些观察结果应在一项大型前瞻性研究中得到验证，以评估囊泡含量在评估疑似ACS患者中的潜在作用。
Aims: Biomarkers are essential in the early detection of acute coronary syndromes (ACS). Serum extracellular vesicles are small vesicles in the plasma containing protein and RNA and have been shown to be involved in ACS-related processes like apoptosis and coagulation. Therefore, we hypothesized that serum extracellular vesicle protein levels are associated with ACS.Methods and results: Three serum extracellular vesicle proteins potentially associated with ACS were identified with differential Q-proteomics and were evaluated in 471 frozen serum samples of ACS-suspected patients presenting to the emergency department (30% of whom had an ACS). Protein levels were measured after vesicle isolation using ExoQuick. Mean serum extracellular vesicle concentration of the different proteins was compared between ACS and non-ACS patients. Selected proteins were tested in a univariate logistic regression model, as well as in a multivariate model to adjust for cardiovascular risk factors. A separate analysis was performed in men and women. In the multivariate logistic regression analysis, polygenic immunoglobulin receptor, (pIgR; OR 1.630, p=0.026), cystatin C (OR 1.641, p=0.021), and complement factor C5a (C5a, OR 1.495, p=0.025) were significantly associated with ACS, while total vesicle protein concentration was borderline significant. The association of the individual proteins with ACS was markedly stronger in men.Conclusions: These data show that serum extracellular vesicle pIgR, cystatin C, and C5a concentrations are independently associated with ACS and that there are pronounced gender differences. These observations should be validated in a large, prospective study to assess the potential role of vesicle content in the evaluation of patients suspected of having an ACS.