Laboratory of Molecular Immunopathology, Clinical Hospital, Federal University of Paraná, Curitiba, PR, Brazil.
Laboratory of Molecular Immunopathology, Clinical Hospital, Federal University of Paraná, Curitiba, PR, Brazil.
Immunol Lett. 2018 Aug;200:18-25. doi: 10.1016/j.imlet.2018.06.006. Epub 2018 Jun 18.
Acute myocardial infarction (AMI) is a potentially fatal condition, being a major cause of death worldwide. Ischemia suffered during AMI causes tissue damage, leading to an inflammatory process. Moreover, myocardial injury can generate damage-associated molecular patterns that activate pattern recognition molecules including some complement proteins.
Here we investigated products of complement activation, C3d and soluble C5b9 (sC5b9), as potential biomarkers for myocardial injury and inflammation, as well as serum cytokines (IL-6 and TNF-alpha), alpha-1-acid glycoprotein (AGP), and classical markers of myocardial necrosis (creatine kinase, creatine kinase-MB isoform, myoglobin and troponin-I) in a longitudinal study of patients with AMI (from admission, 6 h and 12 h post admission, and at discharge from hospital). Individuals undergoing cardiac catheterization (CC) with normal coronary arteries and asymptomatics with no history of cardiovascular disease or invasive procedures were included as controls.
Plasma C3d was higher in AMI at admission, 6 h, 12 h, and discharge vs CC (p < 0.0001; p = 0.0061; p = 0.0081; p = 0.044) and asymptomatic (p = 0.0001 for admission, 6 h and 12 h; p = 0.0002 for discharge). Moreover, sC5b9 was higher only at admission and 6 h vs asymptomatic (p = 0.0031 and p = 0.0019). Additionally, AGP levels were elevated at admission, 6 h, 12 h, and discharge vs asymptomatic (p = 0.0003; p = 0.0289; p = 0.0009, p = 0.0017). IL-6 concentration was low at admission and 6 h and reached a peak at 12 h (p < 0.0001 for all groups). All classical markers of myocardial necrosis presented higher concentration at 6 h.
Our results showed that complement activation is an early event in AMI occurring before the elevation of classical markers of myocardial necrosis such as creatine kinase, creatine kinase-MB isoform, myoglobin and troponin-I. These findings indicated C3d and sC5b9 as possible biomarkers for inflammation and tissue damage in AMI.
急性心肌梗死（AMI）是一种潜在的致命疾病，是全球范围内主要的死亡原因。AMI 期间发生的缺血会导致组织损伤，从而引发炎症过程。此外，心肌损伤会产生损伤相关分子模式，从而激活包括一些补体蛋白在内的模式识别分子。
在这里，我们研究了补体激活产物 C3d 和可溶性 C5b9（sC5b9）作为心肌损伤和炎症的潜在生物标志物，以及血清细胞因子（IL-6 和 TNF-α）、α-1-酸性糖蛋白（AGP）和经典的心肌坏死标志物（肌酸激酶、肌酸激酶同工酶 MB 亚型、肌红蛋白和肌钙蛋白 I），对 AMI 患者进行了一项纵向研究（从入院时、入院后 6 小时和 12 小时以及出院时）。将接受冠状动脉造影（CC）且冠状动脉正常的患者和无心血管疾病或侵入性操作史的无症状患者作为对照。
入院时、入院后 6 小时、入院后 12 小时和出院时 AMI 患者的血浆 C3d 水平高于 CC（p<0.0001；p=0.0061；p=0.0081；p=0.044）和无症状患者（p=0.0001，入院时、入院后 6 小时和 12 小时；p=0.0002，出院时）。此外，仅在入院时和入院后 6 小时 sC5b9 高于无症状患者（p=0.0031 和 p=0.0019）。此外，AGP 水平在入院时、入院后 6 小时、入院后 12 小时和出院时高于无症状患者（p=0.0003；p=0.0289；p=0.0009，p=0.0017）。入院时和入院后 6 小时 IL-6 浓度较低，入院后 12 小时达到峰值（所有组均 p<0.0001）。所有经典的心肌坏死标志物在入院后 6 小时的浓度都较高。
我们的研究结果表明，补体激活是 AMI 的早期事件，发生在肌酸激酶、肌酸激酶同工酶 MB 亚型、肌红蛋白和肌钙蛋白 I 等经典的心肌坏死标志物升高之前。这些发现表明 C3d 和 sC5b9 可能是 AMI 炎症和组织损伤的生物标志物。
