Sidiropoulou Sofia, Gatsiou Aikaterini, Hansson Kenny M, Tsouka Aikaterini N, Stellos Konstantinos, Tselepis Alexandros D
Atherothrombosis Research Centre/Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, 451 10 Ioannina, Greece.
Cardiovascular Disease Prevention Hub, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne NE1 7RU, UK.
Int J Mol Sci. 2024 Dec 12;25(24):13343. doi: 10.3390/ijms252413343.
Ticagrelor, a reversible platelet P2Y receptor antagonist, exerts various pleiotropic actions, some of which are at least partially mediated through adenosine. We studied the ticagrelor and adenosine effect on the angiogenic properties of progenitor CD34-derived endothelial colony-forming cells (ECFCs). Angiogenesis studies were performed in vitro using capillary-like tube formation and spheroid-based angiogenesis assays. The effects of adenosine receptor antagonists, including DPCPX (A antagonist), SCH58621 (A antagonist), MRS1706 (A inverse agonist and antagonist), MRS1220 (A antagonist) and adenosine deaminase (ADA), were also investigated. Ticagrelor, adenosine, and their combination increased capillary-like tube formation and spheroid sprout formation by ECFCs in a dose-dependent manner. This effect was significantly reduced by SCH58621, MRS1706, and their combination, as well as by ADA. By contrast, DPCPX and MRS1220 did not exhibit any inhibitory effects. Similar results were obtained when mature human umbilical vein endothelial cells (HUVECs) were studied. These results show that ticagrelor stimulates angiogenesis by progenitor and mature endothelial cells in an adenosine-dependent pathway in which the adenosine receptors A and A play major roles. The significance of these results at the clinical level in patients with atherothrombotic events and treated with ticagrelor needs to be investigated.
替格瑞洛是一种可逆性血小板P2Y受体拮抗剂，具有多种多效性作用，其中一些作用至少部分是通过腺苷介导的。我们研究了替格瑞洛和腺苷对祖细胞CD34衍生的内皮集落形成细胞（ECFCs）血管生成特性的影响。使用毛细血管样管形成和基于球体的血管生成试验在体外进行血管生成研究。还研究了腺苷受体拮抗剂的作用，包括DPCPX（A受体拮抗剂）、SCH58621（A受体拮抗剂）、MRS1706（A受体反向激动剂和拮抗剂）、MRS1220（A受体拮抗剂）和腺苷脱氨酶（ADA）。替格瑞洛、腺苷及其组合以剂量依赖的方式增加了ECFCs的毛细血管样管形成和球体芽形成。SCH58621、MRS1706及其组合以及ADA显著降低了这种作用。相比之下，DPCPX和MRS1220没有表现出任何抑制作用。在研究成熟人脐静脉内皮细胞（HUVECs）时也获得了类似的结果。这些结果表明，替格瑞洛通过祖细胞和成熟内皮细胞在腺苷依赖性途径中刺激血管生成，其中腺苷受体A和A起主要作用。这些结果在临床层面上对于接受替格瑞洛治疗的动脉粥样硬化血栓形成事件患者的意义需要进一步研究。
