Al-Eitan Laith Naser, Zuhair Saif, Khair Iliya Yacoub, Alghamdi Mansour Abdullah
Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid 22110, Jordan.
Department of Anatomy, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia.
Iran J Basic Med Sci. 2024;27(3):304-310. doi: 10.22038/IJBMS.2023.71819.15605.
The process of vascular formation, also known as angiogenesis, primarily relies on endothelial cell proliferation, migration, and invasion. In recent years, it has been discovered that synthetic cannabinoids (SCs) may potentially impact angiogenic processes within the body. We evaluated the impact of the synthetic cannabinoid (R)-5-Fluoro-ADB on the proliferation rate and angiogenesis in Human Cerebral Microvascular Endothelial Cells (hBMECs).
hBMECs were treated with (R)-5-Fluoro-ADB and investigated for cell viability, migration rate, and tube-like structure formation. Furthermore, angiogenic-related proteins including Angopoitein-1 and -2, and Vascular Endothelial Growth Factors (VEGF) were examined on mRNA and protein levels.
The results showed a notable rise in the rate of proliferation (-value<0.0001) of HBMECs induced by (R)-5-Fluoro-ADB. The angiogenic capacity of HBMECs was also enhanced between 0.001 μM to 1 μM (R)-5-Fluoro-ADB. Moreover, an increase in the levels of ANG-1, ANG-2, and VEGF mRNA and protein, as well as elevated phosphorylation rate of GSK-3β, were observed across various concentrations of (R)-5-Fluoro-ADB.
Our results suggest an innovative approach in pharmacology for addressing a range of conditions linked to angiogenesis. This approach involves precise targeting of both cannabinoid receptors type-1 and -2. To achieve this, specific agonists or antagonists of these receptors could be employed based on the particular characteristics of the diseases in question.
血管形成过程，也称为血管生成，主要依赖于内皮细胞的增殖、迁移和侵袭。近年来，人们发现合成大麻素（SCs）可能会影响体内的血管生成过程。我们评估了合成大麻素（R）-5-氟-ADB对人脑微血管内皮细胞（hBMECs）增殖率和血管生成的影响。
用（R）-5-氟-ADB处理hBMECs，并研究其细胞活力、迁移率和管状结构形成。此外，还在mRNA和蛋白质水平上检测了包括血管生成素-1和-2以及血管内皮生长因子（VEGF）在内的血管生成相关蛋白。
结果显示，（R）-5-氟-ADB诱导的HBMECs增殖率显著提高（P值<0.0001）。在0.001μM至1μM的（R）-5-氟-ADB之间，HBMECs的血管生成能力也得到增强。此外，在不同浓度的（R）-5-氟-ADB中，均观察到ANG-1、ANG-2和VEGF mRNA及蛋白水平的增加，以及GSK-3β磷酸化率的升高。
我们的数据表明了一种药理学上的创新方法，用于解决一系列与血管生成相关的病症。这种方法涉及精确靶向1型和2型大麻素受体。为此，可以根据相关疾病的具体特征使用这些受体的特定激动剂或拮抗剂。
