Cyanate-Impaired Angiogenesis: Association With Poor Coronary Collateral Growth in Patients With Stable Angina and Chronic Total Occlusion.
Cyanate-Impaired Angiogenesis: Association With Poor Coronary Collateral Growth in Patients With Stable Angina and Chronic Total Occlusion.
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氰酸盐血管生成受损：与稳定型心绞痛和慢性完全闭塞患者冠状动脉侧枝生长不良相关
DOI：
10.1161/jaha.116.004700
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发表时间：
2016-12-16
影响因子：
5.4
通讯作者：
Zhang RY
中科院分区：
文献类型：
--
作者：
Sun JT;Yang K;Mao JY;Shen WF;Lu L;Wu QH;Wang YP;Wu LP;Zhang RY
最近，环磷酰胺因其在血管损伤的发病机制中的作用而受到关注。尽管如此，氰酸盐对血管生成的影响仍不清楚。在这项研究中，我们证明了口服氰酸盐会损害小鼠后肢缺血模型的血液灌注恢复。在氰酸盐处理的小鼠的缺血组织中观察到第21天的血液灌注恢复减少。同样，氰酸盐暴露小鼠的缺血后肢组织中毛细血管较少。我们的体外研究表明，氰酸酯及其氨甲酰化产物可抑制内皮细胞的迁移、增殖和管形成能力。进一步的研究表明，氰酸盐通过阻断血管内皮生长因子受体2/磷脂酰肌醇3-激酶/Akt通路来调节血管生成。测定了117例稳定型心绞痛和慢性完全闭塞患者的血清高瓜氨酸（氰酸盐暴露的标志物）浓度。与氰酸盐的抗血管生成作用一致，冠状动脉侧支化不良患者（n=58）中的高瓜氨酸水平高于高侧支化患者（n=59; 21.09±13.08 vs 15.54±9.02 ng/mL，P=0.009）。此外，高瓜氨酸浓度升高是冠状动脉侧支生长不良的强预测因子。氰酸盐诱导的血管生成受损可能导致冠状动脉侧支生长不良。
Cyanate has recently gained attention for its role in the pathogenesis of vascular injury. Nonetheless, the effect of cyanate on angiogenesis remains unclear. In this study, we demonstrated that oral administration of cyanate impaired blood perfusion recovery in a mouse hind‐limb ischemia model. A reduction in blood perfusion recovery at day 21 was observed in the ischemic tissue of cyanate‐treated mice. Likewise, there were fewer capillaries in the ischemic hind‐limb tissue of cyanate‐exposed mice. Our in vitro study showed that cyanate, together with its carbamylated products, inhibited the migration, proliferation, and tube‐formation abilities of endothelial cells. Further research revealed that cyanate regulated angiogenesis partly by interrupting the vascular endothelial growth factor receptor 2/phosphatidylinositol 3‐kinase/Akt pathway. The serum concentrations of homocitrulline, a marker of cyanate exposure, were determined in 117 patients with stable angina and chronic total occlusion. Consistent with the antiangiogenic role of cyanate, homocitrulline levels were increased in patients with poor coronary collateralization (n=58) compared with those with high collateralization (n=59; 21.09±13.08 versus 15.54±9.02 ng/mL, P=0.009). In addition, elevated homocitrulline concentration was a strong predictor of poor coronary collateral growth. Impaired angiogenesis induced by cyanate might contribute to poor coronary collateral growth.