Department of Medicine and Winthrop Research Institute, NYU Winthrop Hospital, 101 Mineola Boulevard, Mineola, NY, 11501, USA.
Am J Cardiovasc Drugs. 2019 Oct;19(5):449-464. doi: 10.1007/s40256-019-00345-5.
Adenosine is an endogenous nucleoside with a short half-life that regulates many physiological functions involving the heart and cardiovascular system. Among the cardioprotective properties of adenosine are its ability to improve cholesterol homeostasis, impact platelet aggregation and inhibit the inflammatory response. Through modulation of forward and reverse cholesterol transport pathways, adenosine can improve cholesterol balance and thereby protect macrophages from lipid overload and foam cell transformation. The function of adenosine is controlled through four G-protein coupled receptors: A, A, A and A. Of these four, it is the A receptor that is in a large part responsible for the anti-inflammatory effects of adenosine as well as defense against excess cholesterol accumulation. A receptor agonists are the focus of efforts by the pharmaceutical industry to develop new cardiovascular therapies, and pharmacological actions of the atheroprotective and anti-inflammatory drug methotrexate are mediated via release of adenosine and activation of the A receptor. Also relevant are anti-platelet agents that decrease platelet activation and adhesion and reduce thrombotic occlusion of atherosclerotic arteries by antagonizing adenosine diphosphate-mediated effects on the P2Y12 receptor. The purpose of this review is to discuss the effects of adenosine on cell types found in the arterial wall that are involved in atherosclerosis, to describe use of adenosine and its receptor ligands to limit excess cholesterol accumulation and to explore clinically applied anti-platelet effects. Its impact on electrophysiology and use as a clinical treatment for myocardial preservation during infarct will also be covered. Results of cell culture studies, animal experiments and human clinical trials are presented. Finally, we highlight future directions of research in the application of adenosine as an approach to improving outcomes in persons with cardiovascular disease.
腺苷是一种内源性核苷，半衰期短，能调节涉及心脏和心血管系统的许多生理功能。腺苷具有改善胆固醇稳态、影响血小板聚集和抑制炎症反应等心脏保护特性。通过调节胆固醇正向和逆向转运途径，腺苷可以改善胆固醇平衡，从而保护巨噬细胞免受脂质过载和泡沫细胞转化。腺苷的功能通过四个 G 蛋白偶联受体：A、A、A 和 A 来控制。在这四个受体中，A 受体在很大程度上负责腺苷的抗炎作用以及抵御过量胆固醇积累。A 受体激动剂是制药行业开发新的心血管治疗方法的重点，抗叶酸类药物甲氨蝶呤的抗动脉粥样硬化和抗炎作用是通过释放腺苷和激活 A 受体来介导的。此外，抗血小板药物通过拮抗二磷酸腺苷对 P2Y12 受体的作用，减少血小板激活和黏附，减少动脉粥样硬化动脉的血栓闭塞，也与本研究相关。本文的目的是讨论腺苷对参与动脉粥样硬化的动脉壁细胞类型的影响，描述腺苷及其受体配体的使用，以限制过量胆固醇的积累，并探讨临床应用的抗血小板作用。还将讨论其对电生理学的影响以及作为心肌梗死后心肌保护的临床治疗方法的应用。本文呈现了细胞培养研究、动物实验和人类临床试验的结果。最后，我们强调了将腺苷作为改善心血管疾病患者预后的一种方法的未来研究方向。
