The Role of Purinergic Signaling in Heart Transplantation

Abstract

Heart transplantation remains the optimal treatment option for patients with end-stage heart disease. Growing evidence demonstrates that purinergic signals mediated by purine nucleotides and nucleosides play vital roles in heart transplantation, especially in the era of ischemia-reperfusion injury (IRI) and allograft rejection. Purinergic signaling consists of extracellular nucleotides and nucleosides, ecto-enzymes, and cell surface receptors; it participates in the regulation of many physiological and pathological processes. During transplantation, excess adenosine triphosphate (ATP) levels are released from damaged cells, and driver detrimental inflammatory responses largely via purinergic P2 receptors. Ecto-nucleosidases sequentially dephosphorylate extracellular ATP to ADP, AMP, and finally adenosine. Adenosine exerts a cardioprotective effect by its anti-inflammatory, antiplatelet, and vasodilation properties. This review focused on the role of purinergic signaling in IRI and rejection after heart transplantation, as well as the clinical applications and prospects of purinergic signaling.

Safety, Tolerability, and Pharmacodynamics of AZD3366 (Optimized Human CD39L3 Apyrase) Alone and in Combination With Ticagrelor and Acetylsalicylic Acid: A Phase 1, Randomized, Placebo‐Controlled Study

“…In addition, the study did not enroll any participants with a history of any clinically important disease, such as cardiovascular disease, who may be of most benefit from AZD3366 therapy. In particular, patients with acute cardiovascular events and ischemia are likely to exhibit higher levels of extracellular tissue ATP and ADP, 23 and the effects of AZD3366 might influence these levels differently when compared with circulating plasma levels in healthy subjects. Therefore, it was not possible to test the tissue‐protective and anti‐inflammatory mode of action of this compound as confirmatory data can be collected only during a phase 2 proof‐of‐concept study in patients with acute myocardial infarction.…”

Advancements in Stimulus-Responsive Co-Delivery Nanocarriers for Enhanced Cancer Immunotherapy

“…33 ATP is generally located inside cells and is an important component of DAMPs. Extracellular ATP participates in purinergic signaling and inflammatory response and is closely associated with diseases such as tumors, ischemic injury, post-heart transplantation, and rejection reactions 34,35 Innate and adaptive immunity are also activated by ATP through a series of reactions. 36,37 Karen M Dwyer's team found that blocking CD39 and CD73 is beneficial for the treatment of acute and chronic kidney diseases.…”