Dabravolski Siarhei A, Kashtalap Vasily V, Utkina Aleksandra S, Babayeva Gulalek A, Maksaeva Anastasia O, Sukhorukov Vasily N, Orekhov Alexander N
Department of Biotechnology Engineering, Braude Academic College of Engineering, Snunit 51, P.O. Box 78, Karmiel, 2161002, Israel.
Research Institute for Complex Issues of Cardiovascular Diseases, 6, Barbarash Boulevard, Kemerovo, 650002, Russia.
J Physiol Biochem. 2025 Jul 16. doi: 10.1007/s13105-025-01108-4.
Atherosclerosis is a complex cardiovascular disease characterised by the accumulation of lipids, inflammatory cells, and fibrous elements within arterial walls, leading to plaque formation and increased risk of cardiovascular events. Recent evidence highlights the pivotal roles of purinergic receptors in mediating the inflammatory and cellular processes associated with atherosclerosis. This review examines the roles of purinergic receptors in the pathophysiology of atherosclerosis, with a particular focus on the P1 subtype (A2A and A3 receptors), the P2X subtype (P2X4 and P2X7 receptors), and the P2Y subtype (P2Y2, P2Y11, and P2Y12 receptors). The A2A and A3 receptors are involved in modulating vascular inflammation, endothelial cell function, and vascular smooth muscle cell calcification. P2X4 has been implicated in the production of pro-inflammatory cytokines and the promotion of plaque inflammation, whereas P2X7 contributes to vascular inflammation, plaque progression, and rupture. The P2Y2 receptor plays critical roles in regulating vascular inflammation and calcification, smooth muscle cell migration, and plaque growth. Furthermore, the P2Y11 receptor has been shown to modulate endothelial cell inflammation, while P2Y12 is associated with lipid accumulation, foam cell formation, vascular smooth muscle cell migration, and plaque development. By synthesising current knowledge on the involvement of purinergic signalling in atherosclerosis, this review discusses potential therapeutic targets for intervention. Specifically, P2Y receptor antagonists present promising avenues for reducing inflammation and improving vascular function in atherosclerotic patients. However, despite the advancements in understanding purinergic receptor functions, challenges remain in translating this knowledge into clinical practice. Further research is essential to unravel the intricate signalling pathways of these receptors and to develop effective biomarker strategies and therapeutic interventions aimed at combatting atherosclerosis and its associated complications.
动脉粥样硬化是一种复杂的心血管疾病，其特征是脂质、炎症细胞和纤维成分在动脉壁内积聚，导致斑块形成并增加心血管事件的风险。最近的证据突出了嘌呤能受体在介导与动脉粥样硬化相关的炎症和细胞过程中的关键作用。本综述探讨了嘌呤能受体在动脉粥样硬化病理生理学中的作用，特别关注P1亚型（A2A和A3受体）、P2X亚型（P2X4和P2X7受体）以及P2Y亚型（P2Y2、P2Y11和P2Y12受体）。A2A和A3受体参与调节血管炎症、内皮细胞功能和血管平滑肌细胞钙化。P2X4与促炎细胞因子的产生和斑块炎症的促进有关，而P2X7则促成血管炎症、斑块进展和破裂。P2Y2受体在调节血管炎症和钙化、平滑肌细胞迁移和斑块生长中起关键作用。此外，已表明P2Y11受体可调节内皮细胞炎症，而P2Y12与脂质积聚、泡沫细胞形成、血管平滑肌细胞迁移和斑块发展有关。通过综合目前关于嘌呤能信号传导参与动脉粥样硬化的知识，本综述讨论了潜在的干预治疗靶点。具体而言，P2Y受体拮抗剂为减少动脉粥样硬化患者的炎症和改善血管功能提供了有前景的途径。然而，尽管在理解嘌呤能受体功能方面取得了进展，但将这些知识转化为临床实践仍面临挑战。进一步的研究对于阐明这些受体复杂的信号通路以及开发有效的生物标志物策略和治疗干预措施以对抗动脉粥样硬化及其相关并发症至关重要。
