Miyakawa Ayumi Aurea, Borin Thaiz Ferraz, Campos Luciene Cristina Gastalho, Girão-Silva Thais, Ribeiro-Silva Joao Carlos, Dallan Luis Alberto Oliveira, Krieger Jose Eduardo
Heart Institute (InCor), University of São Paulo Medical School, São Paulo, SP 05403-000, Brazil.
J Cardiovasc Dev Dis. 2019 Apr 30;6(2):20. doi: 10.3390/jcdd6020020.
The interleukin-1 family is associated with innate immunity and inflammation. The latter has been linked to the genesis of cardiovascular diseases. We, therefore, investigated whether interleukin-1 beta (IL-1β) is activated during arterialization of vein grafts. First, we examined the activation of IL-1β using the rat arterialized jugular vein serially sampled for up to 90 days. IL-1β expression increased 18 times on day 1 in the arterialized rat jugular vein and remained five times above nonarterialized vein levels for up to 90 days. Similarly, IL-1β expression increased early (1-5 days) in human vein graft autopsy samples compared with late phases (1-4 years). Activation was also detected in ex vivo arterialized human saphenous veins. Upon stratification of the results, we uncovered a T allele promoter attenuating effect in IL-1β activation in response to hemodynamic stress. Altogether, the results show that IL-1β is activated during arterialization of vein grafts in rats and humans, and this response is modulated by -511C/T IL-1β gene polymorphism. It is tempting to speculate that the activation of IL-1β, and consequently local inflammation, modulates early vascular remodeling and that the gene polymorphism may be useful in predicting outcomes or assisting in interventions.
白细胞介素-1家族与先天免疫和炎症相关。后者已被证明与心血管疾病的发生有关。因此,我们研究了在静脉移植物动脉化过程中白细胞介素-1β(IL-1β)是否被激活。首先,我们使用连续采样长达90天的大鼠动脉化颈静脉来检测IL-1β的激活情况。在动脉化的大鼠颈静脉中,IL-1β表达在第1天增加了18倍,并在长达90天的时间内保持在非动脉化静脉水平的5倍以上。同样,与后期阶段(1 - 4年)相比,人静脉移植物尸检样本中的IL-1β表达在早期(1 - 5天)增加。在体外动脉化的人隐静脉中也检测到了激活。在对结果进行分层时,我们发现了一个T等位基因启动子在IL-1β对血流动力学应激的激活中具有减弱作用。总体而言,结果表明在大鼠和人的静脉移植物动脉化过程中IL-1β被激活,并且这种反应受到IL-1β基因-511C/T多态性的调节。很容易推测,IL-1β的激活以及由此导致的局部炎症会调节早期血管重塑,并且该基因多态性可能有助于预测结果或辅助干预。