Cardiovascular disease is a major cause of morbidity and mortality worldwide. Innovative new treatment options for this cardiovascular pandemic are urgently needed. Activation of purinergic receptors (PRs) is critically involved in the development and progression of cardiovascular disease including atherosclerosis, ischemic heart disease, hypertension and diabetes. PRs have been targeted for the treatment of several cardiovascular diseases in a clinical setting. The P2Y₁₂R antagonists such as clopidogrel, ticagrelor and others are the most successful class of purinergic drugs targeting platelets for the treatment of acute coronary syndrome. In addition to targeting platelets, ticagrelor may exert P2Y₁₂R-independent effect by targeting erythrocyte-mediated purinergic activation. The partial A1R agonist neladenoson and the A_2AR agonist regadenoson have been applied in cardiovascular medicine. In experimental studies, many other PRs have been shown to play a significant role in the development and progression of cardiovascular diseases, and targeting these receptors have resulted in promising outcomes. Therefore, many of these PRs including A_2BR, A3R, P2X₃R, P2X₄R, P2X₇R, P2Y₁R, P2Y₄R, P2Y₆R and P2Y₁₁R can be considered as therapeutic targets. However, the multitude of PR subtypes expressed in different cells of the cardiovascular system may constitute a challenge whether single or multiple receptors should be targeted at the same time for the best efficacy. The present review discusses the promising purinergic drugs used in clinical studies for the treatment of cardiovascular disease. We also update experimental evidence for many other PRs that can be considered as therapeutic targets for future drug development.

中文翻译：

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更多的嘌呤能受体作为治疗心血管疾病的治疗靶点值得关注。

心血管疾病是全世界发病率和死亡率的主要原因。迫切需要针对这种心血管大流行的创新性新治疗方案。嘌呤能受体（PRs）的激活与心血管疾病（包括动脉粥样硬化，缺血性心脏病，高血压和糖尿病）的发生和发展密切相关。PRs已在临床上针对多种心血管疾病的治疗。P2Y ₁₂ R拮抗剂（例如氯吡格雷，替卡格雷或其他）是针对血小板的嘌呤能药物最成功的一类，用于治疗急性冠状动脉综合征。除靶向血小板外，替格瑞洛还可能产生P2Y ₁₂通过靶向红细胞介导的嘌呤能激活来实现R非依赖性作用。部分A1R激动剂奈拉德森和A _2A R激动剂regadenoson已用于心血管医学。在实验研究中，许多其他PR已显示在心血管疾病的发生和发展中起着重要作用，靶向这些受体已导致有希望的结果。因此，许多PR包括A _2B R，A3R，P2X ₃ R，P2X ₄ R，P2X ₇ R，P2Y ₁ R，P2Y ₄ R，P2Y ₆ R和P2Y ₁₁R可以被认为是治疗靶标。但是，在心血管系统的不同细胞中表达的大量PR亚型可能构成挑战，无论是同时靶向单个或多个受体以获得最佳疗效。本综述讨论了临床研究中用于心血管疾病治疗的有希望的嘌呤能药物。我们还更新了许多其他PR的实验证据，这些PR可被视为未来药物开发的治疗靶标。