University Medical Center Utrecht, Utrecht, The Netherlands.
Eur Heart J Acute Cardiovasc Care. 2013 Mar;2(1):53-60. doi: 10.1177/2048872612471212.
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.
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.
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.
生物标志物对于急性冠状动脉综合征(ACS)的早期检测至关重要。血清细胞外囊泡是血浆中的小囊泡,含有蛋白质和 RNA,已被证明参与 ACS 相关过程,如细胞凋亡和凝血。因此,我们假设血清细胞外囊泡蛋白水平与 ACS 有关。
通过差异 Q-蛋白质组学鉴定了与 ACS 相关的 3 种潜在的血清细胞外囊泡蛋白,并在急诊科就诊的 471 例疑似 ACS 的冷冻血清样本中进行了评估(其中 30%的患者患有 ACS)。使用 ExoQuick 分离囊泡后测量蛋白水平。比较 ACS 患者和非 ACS 患者之间不同蛋白的血清细胞外囊泡浓度。在单变量逻辑回归模型以及调整心血管危险因素的多变量模型中测试了选定的蛋白。对男性和女性分别进行了单独分析。在多变量逻辑回归分析中,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)和补体因子 C5a(C5a,OR 1.495,p=0.025)与 ACS 显著相关,而总囊泡蛋白浓度呈边缘显著。这些蛋白与 ACS 的关联在男性中更为显著。
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,且存在明显的性别差异。这些观察结果应在一项大型前瞻性研究中进行验证,以评估囊泡内容物在评估疑似 ACS 患者中的潜在作用。