Teng Bunyen, Smith Jonathan D, Rosenfeld Michael E, Robinet Peggy, Davis Mary E, Morrison R Ray, Mustafa S Jamal
Department of Physiology and Pharmacology, Center for Cardiovascular and Respiratory Sciences, West Virginia University, 1 Medical Center Drive, Morgantown, WV, USA.
Cardiovasc Res. 2014 Apr 1;102(1):157-65. doi: 10.1093/cvr/cvu033. Epub 2014 Feb 12.
The goal of this study was to determine whether the A1 adenosine receptor (AR) plays a role in atherosclerosis development and to explore its potential mechanisms.
Double knockout (DKO) mice, deficient in the genes encoding A1 AR and apolipoprotein E (apoE), demonstrated reduced atherosclerotic lesions in aortic arch (en face), aortic root, and innominate arteries when compared with apoE-deficient mice (APOE-KO) of the same age. Treating APOE-KO with an A1 AR antagonist (DPCPX) also led to a concentration-dependent reduction in lesions. The total plasma cholesterol and triglyceride levels were not different between DKO and APOE-KO; however, higher triglyceride was observed in DKO fed a high-fat diet. DKO also had higher body weights than APOE-KO. Plasma cytokine concentrations (IL-5, IL-6, and IL-13) were significantly lower in DKO. Proliferating cell nuclear antigen expression was also significantly reduced in the aorta from DKO. Despite smaller lesions in DKO, the composition of the innominate artery lesion and cholesterol loading and efflux from bone marrow-derived macrophages of DKO were not different from APOE-KO.
The A1 AR may play a role in the development of atherosclerosis, possibly due to its pro-inflammatory and mitogenic properties.
本研究旨在确定A1腺苷受体（AR）是否在动脉粥样硬化发展中发挥作用，并探索其潜在机制。
与同年龄的载脂蛋白E缺陷小鼠（APOE-KO）相比，编码A1 AR和载脂蛋白E（apoE）的基因双敲除（DKO）小鼠在主动脉弓（正面）、主动脉根部和无名动脉中的动脉粥样硬化病变减少。用A1 AR拮抗剂（DPCPX）处理APOE-KO也导致病变呈浓度依赖性减少。DKO和APOE-KO之间的总血浆胆固醇和甘油三酯水平没有差异；然而，在喂食高脂饮食的DKO中观察到甘油三酯较高。DKO的体重也高于APOE-KO。DKO中的血浆细胞因子浓度（IL-5、IL-6和IL-13）显著降低。DKO主动脉中增殖细胞核抗原的表达也显著降低。尽管DKO中的病变较小，但其无名动脉病变的组成以及DKO骨髓来源巨噬细胞的胆固醇负荷和流出与APOE-KO没有差异。
A1 AR可能在动脉粥样硬化的发展中起作用，可能是由于其促炎和促有丝分裂特性。
