Purpose

Estrogens have beneficial effects on the cardiovascular system, promoting vasodilation, endothelial cells growth, relaxation, and regulation of blood pressure. Some of these effects could be associated with the purinergic system known for the control of vasodilation, inflammation, and platelet function. The aim of our study was the evaluation of ATP, AMP, and adenosine extracellular catabolism, catalyzed by ectonucleoside triphosphate diphosphohydrolase-1 (CD39), ecto-5′-nucleotidase (CD73), and ecto-adenosine deaminase (eADA) in mouse aortas.

Methods

Extracellular hydrolysis of ATP, AMP, and adenosine was estimated on the aortic surface of 3-month-old female and male C57BL/6 J wild-type (WT) mice, in female WT mouse aortas incubated for 48 h in the presence or absence of 100 nM estradiol, and in WT female mouse and ApoE-/-LDL-R-/- aortas. The conversion of substrates to products was analyzed by high-pressure liquid chromatography (HPLC).

Results

We demonstrated significantly higher adenosine deamination rate in WT male vs. female mice (p = 0.041). We also noted the lower adenosine hydrolysis in aortas exposed to estradiol, as compared with the samples incubated in estradiol-free medium (p = 0.043). Finally, we observed that adenosine conversion to inosine was significantly higher on the surface of ApoE-/-LDL-R-/- aortas compared with WT mice (p = 0.001). No such effects were noted in ATP and AMP extracellular hydrolysis.

Conclusion

We conclude that estradiol inhibits the extracellular degradation of adenosine to inosine, which may be an element of its vascular protective effect, as it will lead to an increase in extracellular adenosine concentration. We can also assume that during the development of the atherosclerotic process, the protective role of estradiol in the regulation of adenosine degradation may be obscured by other pathogenic factors.

中文翻译：

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雌二醇对血管细胞外核苷酸代谢酶的影响。

目的

雌激素对心血管系统具有有益作用，可促进血管舒张、内皮细胞生长、放松和调节血压。其中一些作用可能与以控制血管舒张、炎症和血小板功能而闻名的嘌呤能系统有关。我们研究的目的是评估 ATP、AMP 和腺苷细胞外分解代谢，由外核苷三磷酸二磷酸水解酶-1 (CD39)、外核苷 5'-核苷酸酶 (CD73) 和外腺苷脱氨酶 (eADA) 在小鼠主动脉中催化.

方法

在 3 个月大的雌性和雄性 C57BL/6 J 野生型 (WT) 小鼠的主动脉表面上，在存在或不存在的情况下孵育 48 小时的雌性 WT 小鼠主动脉中，估计了 ATP、AMP 和腺苷的细胞外水解100 nM 雌二醇，在 WT 雌性小鼠和 ApoE-/-LDL-R-/- 主动脉中。通过高压液相色谱（HPLC）分析底物向产物的转化。

结果

我们在 WT 雄性与雌性小鼠中证明了显着更高的腺苷脱氨率 ( p  = 0.041)。我们还注意到，与在不含雌二醇的培养基中孵育的样品相比，暴露于雌二醇的主动脉中腺苷水解较低 ( p  = 0.043)。最后，我们观察到与 WT 小鼠相比，ApoE-/-LDL-R-/- 主动脉表面的腺苷转化为肌苷显着更高（p  = 0.001）。在 ATP 和 AMP 细胞外水解中没有注意到这种影响。

结论

我们得出结论，雌二醇抑制细胞外腺苷降解为肌苷，这可能是其血管保护作用的一个因素，因为它会导致细胞外腺苷浓度增加。我们还可以假设，在动脉粥样硬化过程的发展过程中，雌二醇在调节腺苷降解中的保护作用可能会被其他致病因素所掩盖。