Kalamatianos Theodosis, Drosos Evangelos, Magkrioti Christiana, Nikitopoulou Ioanna, Koutsarnakis Christos, Kotanidou Anastasia, Paraskevas George P, Aidinis Vassilis, Stranjalis George
Department of Neurosurgery, Faculty of Health Sciences, School of Medicine, Evaggelismos General Hospital, National and Kapodistrian University of Athens, 106 76 Athens, Greece.
Hellenic Centre for Neurosurgery Research, "Professor Petros S. Kokkalis", 106 75 Athens, Greece.
Diagnostics (Basel). 2022 Aug 2;12(8):1865. doi: 10.3390/diagnostics12081865.
Autotaxin (ATX) is the ectoenzyme producing the bulk of lysophosphatidic acid (LPA) in circulation. ATX and LPA-mediated signaling (the ATX-LPA axis) play critical roles in the vascular and nervous system development. In adults, this axis contributes to diverse processes, including coagulation, inflammation, fibroproliferation and angiogenesis under physiological and/or pathophysiological conditions. Given evidence implicating several of these processes in chronic subdural hematoma (CSDH) pathogenesis and development, we assessed ATX activity in CSDH patients. Twenty-eight patients were recruited. Blood and hematoma fluid were collected. Enzymatic assays were used to establish serum and hematoma ATX activity. Enzyme-linked immunosorbent assays were used to establish hematoma beta trace (BT) levels, a cerebrospinal fluid (CSF) marker, in a hematoma. ATX activity was nearly three folds higher in hematoma compared to serum (P < 0.001). There was no significant correlation between BT levels and ATX activity in a hematoma. The present results show, for the first time, that ATX is catalytically active in the hematoma fluid of CSDH patients. Moreover, our findings of significantly elevated ATX activity in hematoma compared to serum, implicate the ATX-LPA axis in CSDH pathophysiology. The CSF origin of ATX could not be inferred with the present results. Additional research is warranted to establish the significance of the ATX-LPA axis in CSDH and its potential as a biomarker and/or therapeutic target.
自分泌运动因子(ATX)是循环中产生大部分溶血磷脂酸(LPA)的胞外酶。ATX和LPA介导的信号传导(ATX-LPA轴)在血管和神经系统发育中起关键作用。在成年人中,该轴在生理和/或病理生理条件下参与多种过程,包括凝血、炎症、纤维增殖和血管生成。鉴于有证据表明这些过程中的几个与慢性硬膜下血肿(CSDH)的发病机制和发展有关,我们评估了CSDH患者的ATX活性。招募了28名患者。采集血液和血肿液。采用酶法测定血清和血肿中的ATX活性。采用酶联免疫吸附测定法测定血肿中脑脊液(CSF)标志物β-微量蛋白(BT)的水平。与血清相比,血肿中的ATX活性高出近三倍(P < 0.001)。血肿中BT水平与ATX活性之间无显著相关性。本研究结果首次表明,ATX在CSDH患者的血肿液中具有催化活性。此外,我们发现血肿中的ATX活性明显高于血清,这表明ATX-LPA轴参与了CSDH的病理生理过程。目前的结果无法推断ATX的脑脊液来源。有必要进行进一步的研究,以确定ATX-LPA轴在CSDH中的意义及其作为生物标志物和/或治疗靶点的潜力。