Tillmanns Jochen, Widera Christian, Habbaba Yasmin, Galuppo Paolo, Kempf Tibor, Wollert Kai C, Bauersachs Johann
Department of Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany.
Int J Cardiol. 2013 Oct 9;168(4):3926-31. doi: 10.1016/j.ijcard.2013.06.061. Epub 2013 Aug 6.
Fibroblast activation protein α (FAP) is a membrane glycoprotein with dipeptidyl-peptidase and collagenase activity and is expressed in cancer, arthritis, and atherosclerotic plaques. We hypothesized that FAP can be measured quantitatively in the circulation and provide prognostic information in acute coronary syndrome (ACS).
We assessed the performance of a commercially available FAP ELISA and the pre-analytic characteristics of the marker. We determined FAP concentrations in EDTA plasma samples from 101 apparently healthy blood donors and 407 patients with ACS. Patients were followed for 12 months regarding all-cause mortality and non-fatal myocardial infarction (MI).
FAP was stable at room temperature (for 1 day) and 4°C (3 days) and resistant to 3 freeze/thaw cycles. Recovery of recombinant human FAP ranged from 78 to 103% and serial dilutions of spiked samples resulted in measurements within 91 to 120% of expected values. Patients with ACS had lower plasma FAP concentrations compared with blood donors [median (25th-75th percentiles): 84 (69-101) ng/mL vs. 108 (87-124) ng/mL, P < 0.001]. Patients presenting with FAP concentrations in the first quartile had a 3.0-fold higher risk of death (95% confidence interval 1.4-6.2) compared with patients in the second to fourth quartiles (P = 0.004). FAP concentration was not related to the risk of MI.
Our study is the first to associate FAP with prognosis in ACS. The favorable pre-analytic characteristics of FAP will facilitate future studies of the marker in other disease settings associated with altered FAP expression.
成纤维细胞活化蛋白α(FAP)是一种具有二肽基肽酶和胶原酶活性的膜糖蛋白,在癌症、关节炎和动脉粥样硬化斑块中表达。我们假设FAP可在循环中进行定量测量,并为急性冠状动脉综合征(ACS)提供预后信息。
我们评估了一种市售FAP酶联免疫吸附测定(ELISA)的性能以及该标志物的分析前特征。我们测定了101名表面健康的献血者和407例ACS患者的乙二胺四乙酸(EDTA)血浆样本中的FAP浓度。对患者进行了为期12个月的全因死亡率和非致命性心肌梗死(MI)随访。
FAP在室温(1天)和4°C(3天)下稳定,并且耐受3次冻融循环。重组人FAP的回收率在78%至103%之间,加标样本的系列稀释测量值在预期值的91%至120%范围内。与献血者相比,ACS患者的血浆FAP浓度较低[中位数(第25 - 75百分位数):84(69 - 101)ng/mL对108(87 - 124)ng/mL,P < 0.001]。与第二至第四四分位数的患者相比,FAP浓度处于第一四分位数的患者死亡风险高3.0倍(95%置信区间1.4 - 6.2)(P = 0.004)。FAP浓度与MI风险无关。
我们的研究首次将FAP与ACS的预后相关联。FAP良好的分析前特征将有助于未来在其他与FAP表达改变相关的疾病背景下对该标志物的研究。