Tillmanns Jochen, Fraccarollo Daniela, Galuppo Paolo, Wollert Kai C, Bauersachs Johann
Department of Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany.
Department of Cardiology and Angiology, Hannover Medical School, 30625 Hannover, Germany.
Int J Cardiol. 2017 Apr 1;232:155-159. doi: 10.1016/j.ijcard.2017.01.037. Epub 2017 Jan 5.
Fibroblast activation protein alpha (FAP) is a membrane-bound serine protease expressed by activated fibroblasts after myocardial infarction (MI). Reduced circulating FAP levels were associated with increased mortality in patients with acute coronary syndrome. We hypothesized that FAP concentrations are altered after acute ST-elevation MI (STEMI), and related to myocardial damage.
We measured circulating FAP concentrations in blood plasma of 60 patients on admission, day 1, day 3 and day 5 after STEMI, and in 25 apparently healthy blood donors as controls.
Plasma FAP concentrations were lower in STEMI patients on admission (71ng/mL) than in blood donors (101ng/mL, P<0.0001). FAP concentrations declined in STEMI patients from admission to day 3 (66ng/mL, P<0.05) and day 5 (57ng/mL, P<0.05). FAP concentrations on day 5 were inversely correlated with maximum CK and maximum CRP levels. In a multiple linear regression analysis, maximum CRP was independently associated with low FAP concentrations on day 5 after STEMI. When stratified according to the absolute amount of FAP change from admission to day 5 (ΔFAP), patients with high ΔFAP (-22ng/mL) had worse left ventricular function, higher levels of hs-cTnT, CK on admission, maximum CK and CRP than patients with low ΔFAP (-3ng/mL).
Our study first demonstrates alterations of circulating FAP concentrations acutely after STEMI. A greater decline of circulating FAP concentrations in the first 5days after STEMI is associated with increased myocardial damage and inflammation. Measurement of circulating FAP might help to better understand the relation of myocardial injury and inflammatory response in the individual patient.
成纤维细胞活化蛋白α（FAP）是一种膜结合丝氨酸蛋白酶，在心肌梗死（MI）后由活化的成纤维细胞表达。急性冠状动脉综合征患者循环中FAP水平降低与死亡率增加相关。我们推测急性ST段抬高型心肌梗死（STEMI）后FAP浓度会发生改变，且与心肌损伤有关。
我们测量了60例STEMI患者入院时、发病第1天、第3天和第5天血浆中的循环FAP浓度，并以25名明显健康的献血者作为对照。
STEMI患者入院时血浆FAP浓度（71ng/mL）低于献血者（101ng/mL，P<0.0001）。STEMI患者从入院到第3天（66ng/mL，P<0.05）和第5天（57ng/mL，P<0.05）FAP浓度下降。第5天的FAP浓度与最大肌酸激酶（CK）和最大C反应蛋白（CRP）水平呈负相关。在多元线性回归分析中，最大CRP与STEMI后第5天的低FAP浓度独立相关。根据从入院到第5天FAP变化的绝对量（ΔFAP）进行分层时，与低ΔFAP（-3ng/mL）的患者相比，高ΔFAP（-22ng/mL）的患者左心室功能更差，入院时高敏心肌肌钙蛋白T（hs-cTnT）、CK、最大CK和CRP水平更高。
我们的研究首次证明STEMI后循环FAP浓度会急性改变。STEMI后前5天循环FAP浓度下降幅度更大与心肌损伤和炎症增加相关。测量循环FAP可能有助于更好地理解个体患者中心肌损伤与炎症反应的关系。
