Starke Andreas, Kollikowski Alexander M, Vogt Vivian, Stoll Guido, Nieswandt Bernhard, Pham Mirko, Stegner David, Schuhmann Michael K
Rudolf Virchow Center for Integrative and Translational Imaging, Julius-Maximilians-Universität Würzburg (JMU), 97080 Würzburg, Germany.
Department of Neuroradiology, University Hospital Würzburg, 97080 Würzburg, Germany.
Biomedicines. 2024 Sep 26;12(10):2191. doi: 10.3390/biomedicines12102191.
Severe acute ischemic stroke (AIS) is mainly caused by thromboembolism originating from symptomatic carotid artery (ICA) stenosis or in the heart due to atrial fibrillation. Glycoprotein VI (GPVI), a principal platelet receptor, facilitates platelet adherence and thrombus formation at sites of vascular injury such as symptomatic ICA stenosis. The shedding of GPVI from the platelet surface releases soluble GPVI (sGPVI) into the circulation. Here, we aimed to determine whether sGPVI can serve as a local biomarker to differentiate between local atherosclerotic and systemic cardiac thromboembolism in AIS. We conducted a cohort study involving 105 patients undergoing emergency endovascular thrombectomy (EVT) for anterior circulation stroke. First, sGPVI concentrations were measured in systemic arterial plasma samples collected at the ipsilateral ICA level, including groups with significantly (≥50%) stenotic and non-stenotic arteries. A second sample, taken from the intracerebral pial circulation, was used to assess GPVI shedding locally within the ischemic brain. Our analysis revealed no significant increase in systemic sGPVI levels in patients with symptomatic ≥ 50% ICA stenosis (3.2 [95% CI 1.5-5.0] ng/mL; = 33) compared with stroke patients without significant ICA stenosis (3.2 [95% CI 2.3-4.2] ng/mL; = 72). Additionally, pial blood samples, reflecting intravascular molecular conditions during collateral flow, showed similar sGPVI levels when compared to the systemic ICA samples in both groups. Our findings indicate that GPVI is not locally cleaved and shed into the bloodstream in significant amounts during hyper-acute ischemic stroke, neither at the level of symptomatic ICA nor intracranially during collateral blood supply. Therefore, sGPVI does not appear to be suitable as a local stroke biomarker despite strong evidence of a major role for GPVI-signaling in stroke pathophysiology.
严重急性缺血性卒中（AIS）主要由症状性颈动脉（ICA）狭窄或心房颤动导致的心脏血栓栓塞引起。糖蛋白VI（GPVI）是主要的血小板受体，可促进血小板在血管损伤部位（如症状性ICA狭窄处）的黏附和血栓形成。GPVI从血小板表面脱落会将可溶性GPVI（sGPVI）释放到循环中。在此，我们旨在确定sGPVI是否可作为一种局部生物标志物，用于区分AIS中的局部动脉粥样硬化性血栓栓塞和全身性心脏血栓栓塞。我们进行了一项队列研究，纳入了105例因前循环卒中接受急诊血管内血栓切除术（EVT）的患者。首先，在同侧ICA水平采集的全身动脉血浆样本中测量sGPVI浓度，样本包括动脉显著（≥50%）狭窄组和非狭窄组。从脑软膜循环采集的第二个样本用于评估缺血性脑内局部的GPVI脱落情况。我们的分析显示，与无显著ICA狭窄的卒中患者（3.2 [95% CI 2.3 - 4.2] ng/mL；n = 72）相比，症状性ICA狭窄≥50%的患者全身sGPVI水平无显著升高（3.2 [95% CI 1.5 - 5.0] ng/mL；n = 33）。此外，反映侧支血流期间血管内分子状况的软膜血样本与两组的全身ICA样本相比，sGPVI水平相似。我们的研究结果表明，在超急性缺血性卒中期间，无论是在症状性ICA水平还是在侧支供血期间的颅内，GPVI都不会大量局部裂解并释放到血液中。因此，尽管有强有力的证据表明GPVI信号在卒中病理生理学中起主要作用，但sGPVI似乎并不适合作为局部卒中生物标志物。
