From the Department of Internal Medicine, Division of Cardiovascular Medicine (N.R.S., D.B., K.M.M., A.M., I.M.R., D.R.G., D.J.P.), University of Michigan Medical Center, Ann Arbor.
Division of Pulmonary and Critical Care (A.L.M.), University of Michigan Medical Center, Ann Arbor.
Arterioscler Thromb Vasc Biol. 2020 Jan;40(1):61-71. doi: 10.1161/ATVBAHA.119.313002. Epub 2019 Oct 17.
CD73 is an ectonucleotidase which catalyzes the conversion of AMP (adenosine monophosphate) to adenosine. Adenosine has been shown to be anti-inflammatory and vasorelaxant. The impact of ectonucleotidases on age-dependent atherosclerosis remains unclear. Our aim was to investigate the role of CD73 in age-dependent accumulation of atherosclerosis. Approach and results: Mice doubly deficient in CD73 and ApoE (apolipoprotein E; () were generated, and the extent of aortic atherosclerotic plaque was compared with controls at 12, 20, 32, and 52 weeks. By 12 weeks of age, mice exhibited a significant increase in plaque (1.4±0.5% of the total vessel surface versus 0.4±0.1% in controls, <0.005). By 20 weeks of age, this difference disappeared (2.9±0.4% versus 3.3±0.7%). A significant reversal in phenotype emerged at 32 weeks (9.8±1.2% versus 18.3±1.4%; <0.0001) and persisted at the 52 week timepoint (22.4±2.1% versus 37.0±2.1%; <0.0001). The inflammatory response to aging was found to be comparable between mice and controls. A reduction in lipolysis in CD73 competent mice was observed, even with similar plasma lipid levels ( versus at 12 weeks [16.2±0.7 versus 9.5±1.4 nmol glycerol/well], 32 weeks [24.1±1.5 versus 7.4±0.4 nmol/well], and 52 weeks [13.8±0.62 versus 12.7±2.0 nmol/well], <0.001).
At early time points, CD73 exerts a subtle antiatherosclerotic influence, but with age, the pattern reverses, and the presence of CD73 promoted suppression of lipid catabolism.
CD73 是一种外核苷酸酶，可催化 AMP（单磷酸腺苷）转化为腺苷。已证明腺苷具有抗炎和血管舒张作用。外核苷酸酶对年龄相关性动脉粥样硬化的影响尚不清楚。我们的目的是研究 CD73 在年龄相关性动脉粥样硬化积累中的作用。
生成了 CD73 和载脂蛋白 E（ApoE；）双重缺陷的小鼠，并比较了 12、20、32 和 52 周时主动脉粥样硬化斑块的程度与 对照组。12 周龄时，与 对照组（0.4±0.1%）相比，小鼠的斑块显著增加（1.4±0.5%），<0.005。20 周龄时，这种差异消失（2.9±0.4%与 3.3±0.7%）。32 周时，表型出现显著逆转（9.8±1.2%与 18.3±1.4%，<0.0001），并持续至 52 周（22.4±2.1%与 37.0±2.1%，<0.0001）。发现衰老引起的炎症反应在 小鼠和 对照组之间相似。即使血浆脂质水平相似，也观察到 CD73 功能正常的小鼠脂肪分解减少（12 周时为 （16.2±0.7 与 9.5±1.4 nmol 甘油/孔），32 周时为 （24.1±1.5 与 7.4±0.4 nmol/孔），52 周时为 （13.8±0.62 与 12.7±2.0 nmol/孔），<0.001）。
在早期阶段，CD73 发挥微妙的抗动脉粥样硬化作用，但随着年龄的增长，这种模式发生逆转，CD73 的存在促进了脂质分解代谢的抑制。
