1 Department of Cardiovascular Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
2 Education and Research Support Center, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
Eur Heart J Acute Cardiovasc Care. 2018 Sep;7(6):561-569. doi: 10.1177/2048872616683635. Epub 2016 Dec 22.
Acute myocardial infarction (AMI) induces marked activation of the sympathetic nervous system. Fatty acid binding protein 4 (FABP4) is not only an intracellular protein, but also a secreted adipokine that contributes to obesity-related metabolic complications. Here, we examined the role of serum FABP4 as a pathophysiological marker in patients with AMI.
We studied 106 patients presenting to the emergency unit with a final diagnosis of AMI, including 12 patients resuscitated from out-of-hospital cardiac arrest (OHCA) caused by ventricular fibrillation. FABP4 levels peaked on admission or just after percutaneous coronary intervention and declined thereafter. Regression analysis revealed no significant correlation between peak FABP4 and peak cardiac troponin T determined by Roche high-sensitive assays (hs-TnT). Notably, FABP4 levels were particularly elevated in AMI patients who were resuscitated from OHCA (median 130.2 ng/mL, interquartile range (IQR) 51.8-243.9 ng/mL) compared with those without OHCA (median 26.1 ng/ml, IQR 17.1-43.4 ng/mL), while hs-TnT levels on admission were not associated with OHCA. Immunohistochemistry of the human heart revealed that FABP4 is abundantly present in adipocytes within myocardial tissue and epicardial adipose tissue. An in vitro study using cultured adipocytes showed that FABP4 is released through a β3-adrenergic receptor (AR)-mediated mechanism.
FABP4 levels were significantly elevated during the early hours after the onset of AMI and were robustly increased in OHCA survivors. Together with the finding that FABP4 is released from adipocytes via β3-AR-mediated lipolysis, our data provide a novel hypothesis that serum FABP4 may represent the adrenergic overdrive that accompanies acute cardiovascular disease, including AMI.
急性心肌梗死（AMI）会引起交感神经系统的显著激活。脂肪酸结合蛋白 4（FABP4）不仅是一种细胞内蛋白，还是一种分泌型脂肪因子，可导致与肥胖相关的代谢并发症。在此，我们研究了血清 FABP4 作为 AMI 患者病理生理标志物的作用。
我们研究了 106 例因室颤导致的院外心脏骤停（OHCA）而被复苏的 AMI 患者，包括在急诊科就诊的最终诊断为 AMI 的 12 例患者。FABP4 水平在入院时或经皮冠状动脉介入治疗后即刻达到峰值，随后下降。回归分析显示，FABP4 峰值与罗氏高敏检测法（hs-TnT）确定的肌钙蛋白 T 峰值之间无显著相关性。值得注意的是，与无 OHCA 的 AMI 患者相比，从 OHCA 中复苏的 AMI 患者的 FABP4 水平显著升高（中位数 130.2ng/ml，四分位距 IQR 51.8-243.9ng/ml），而入院时的 hs-TnT 水平与 OHCA 无关。对人心组织的免疫组化染色显示，FABP4 在心肌组织和心外膜脂肪组织的脂肪细胞中大量存在。对培养的脂肪细胞进行的体外研究表明，FABP4 通过β3-肾上腺素能受体（AR）介导的机制释放。
AMI 发病后早期 FABP4 水平显著升高，在 OHCA 幸存者中明显升高。与 FABP4 通过β3-AR 介导的脂肪分解从脂肪细胞中释放的发现一起，我们的数据提供了一个新的假说，即血清 FABP4 可能代表伴随急性心血管疾病（包括 AMI）的肾上腺素能过度驱动。
