Al-Eitan Laith, Kharmah Hana Abu
Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid, 22110, Jordan.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Feb;398(2):1613-1624. doi: 10.1007/s00210-024-03322-1. Epub 2024 Aug 13.
Angiogenesis is the process by which blood vessels are generated from preexisting ones. Synthetic cannabinoids represent new psychoactive substances that bind to the cannabinoid receptor 1 (CB1R) and cannabinoid receptor 2 (CB2R) and simulate similar effects of tetrahydrocannabinol, the primary component found in cannabis. In the present study, we used the synthetic cannabinoid EMB-FUBINACA to study its impact on brain angiogenesis. Human brain microvascular endothelial cells (HBMECs) were cultivated in DMEM media before being subjected to different concentrations of EMB-FUBINACA and the control. Cell viability and the migration rates of HBMECs were evaluated using the viability and wound healing assays, respectively. An in vitro Matrigel Tube Formation Assay was carried out to measure the angiogenic capacity of endothelial cells. Angiopoietin-1 (ANG-1), Angiopoietin-2 (ANG-2), and vascular endothelial growth factor (VEGF) mRNA expression were detected using Real-Time PCR. The released VEGF, ANG-1, and ANG-2 concentrations were detected using ELISA. Western blotting was performed to measure the levels of phosphorylated GSK-3β, VEGF, ANG-1, and ANG-2. EMB-FUBINACA stimulated endothelial cell proliferation, migration, and capillary tube-like formation and promoted the expression of proangiogenic factors on RNA and protein levels. This study points out that the synthetic cannabinoid EMB-FUBINACA is a potential candidate for further investigations to confirm its potential as an inducer of brain angiogenesis. This could encourage researchers to create a new therapeutic approach for angiogenesis-related diseases.
血管生成是从已有的血管中生成新血管的过程。合成大麻素是一类新型精神活性物质，它们与大麻素受体1（CB1R）和大麻素受体2（CB2R）结合，并模拟大麻中主要成分四氢大麻酚的类似作用。在本研究中，我们使用合成大麻素EMB - FUBINACA来研究其对脑微血管生成的影响。人脑血管内皮细胞（HBMECs）在DMEM培养基中培养，然后分别用不同浓度的EMB - FUBINACA和对照组进行处理。分别使用细胞活力测定法和伤口愈合试验评估HBMECs的细胞活力和迁移率。进行体外基质胶管形成试验以测量内皮细胞的血管生成能力。使用实时PCR检测血管生成素-1（ANG-1）、血管生成素-2（ANG-2）和血管内皮生长因子（VEGF）的mRNA表达。使用酶联免疫吸附测定法检测释放的VEGF、ANG-1和ANG-2浓度。进行蛋白质印迹法以测量磷酸化GSK-3β、VEGF、ANG-1和ANG-2的水平。EMB - FUBINACA刺激内皮细胞增殖、迁移和毛细血管样形成，并在RNA和蛋白质水平上促进促血管生成因子的表达。本研究指出，合成大麻素EMB - FUBINACA是进一步研究以确认其作为脑微血管生成诱导剂潜力的潜在候选物。这可能会鼓励研究人员为血管生成相关疾病创造一种新的治疗方法。
