From the Department of Vascular Surgery (J.J., H.H.) and Heart Center (T.K.), Turku University Hospital, Turku, Finland; Medicity Research Laboratory, Department of Microbiology and Immunology, University of Turku, Turku, Finland (G.G.Y., M.H., K.A., S.J.); and National Institute for Health and Welfare, Helsinki, Finland (V.S.).
Circ Res. 2015 Mar 27;116(7):1206-15. doi: 10.1161/CIRCRESAHA.116.305715. Epub 2015 Feb 2.
Purinergic signaling plays an important role in inflammation and vascular integrity, but little is known about purinergic mechanisms during the pathogenesis of atherosclerosis in humans.
The objective of this study is to study markers of purinergic signaling in a cohort of patients with peripheral artery disease.
Plasma ATP and ADP levels and serum nucleoside triphosphate diphosphohydrolase-1 (NTPDase1/CD39) and ecto-5'-nucleotidase/CD73 activities were measured in 226 patients with stable peripheral artery disease admitted for nonurgent invasive imaging and treatment. The major findings were that ATP, ADP, and CD73 values were higher in atherosclerotic patients than in controls without clinically evident peripheral artery disease (P<0.0001). Low CD39 activity was associated with disease progression (P=0.01). In multivariable linear regression models, high CD73 activity was associated with chronic hypoxia (P=0.001). Statin use was associated with lower ADP (P=0.041) and tended to associate with higher CD73 (P=0.054), while lower ATP was associated with the use of angiotensin receptor blockers (P=0.015).
Purinergic signaling plays an important role in peripheral artery disease progression. Elevated levels of circulating ATP and ADP are especially associated with atherosclerotic diseases of younger age and smoking. The antithrombotic and anti-inflammatory effects of statins may partly be explained by their ability to lower ADP. We suggest that the prothrombotic nature of smoking could be a cause of elevated ADP, and this may explain why cardiovascular patients who smoke benefit from platelet P2Y12 receptor antagonists more than their nonsmoking peers.
嘌呤能信号在炎症和血管完整性中发挥着重要作用，但人们对人类动脉粥样硬化发病机制中的嘌呤能机制知之甚少。
本研究旨在研究嘌呤能信号在周围动脉疾病患者队列中的标志物。
在 226 名因非紧急有创影像学和治疗而入院的稳定型周围动脉疾病患者中，测量了血浆 ATP 和 ADP 水平以及血清核苷三磷酸二磷酸水解酶-1（NTPDase1/CD39）和外切 5'-核苷酸酶/CD73 活性。主要发现是，与无临床明显外周动脉疾病的对照组相比，动脉粥样硬化患者的 ATP、ADP 和 CD73 值更高（P<0.0001）。低 CD39 活性与疾病进展相关（P=0.01）。在多变量线性回归模型中，高 CD73 活性与慢性缺氧相关（P=0.001）。他汀类药物的使用与 ADP 降低相关（P=0.041），且与 CD73 升高相关（P=0.054），而低 ATP 与血管紧张素受体阻滞剂的使用相关（P=0.015）。
嘌呤能信号在周围动脉疾病的进展中起着重要作用。循环中 ATP 和 ADP 水平升高尤其与年龄较小和吸烟的动脉粥样硬化疾病相关。他汀类药物的抗血栓和抗炎作用部分可以通过降低 ADP 来解释。我们认为，吸烟的促血栓形成特性可能是 ADP 升高的原因，这可以解释为什么吸烟的心血管患者比不吸烟的患者更受益于血小板 P2Y12 受体拮抗剂。
