体内核苷逆转录酶抑制剂诱导小静脉和小动脉白细胞-内皮细胞相互作用的特征。
Profile of leukocyte-endothelial cell interactions induced in venules and arterioles by nucleoside reverse-transcriptase inhibitors in vivo.
机构信息
Departamento de Farmacología and CIBERehd, Facultad de Medicina, Universidad de Valencia.
出版信息
J Infect Dis. 2013 Nov 1;208(9):1448-53. doi: 10.1093/infdis/jit340. Epub 2013 Aug 1.
BACKGROUND
There is controversy regarding cardiovascular (CV) toxicity of the nucleoside reverse-transcriptase inhibitors used to treat human immunodeficiency virus infection.
METHODS
We evaluated the effects of nucleoside reverse-transcriptase inhibitors on leukocyte-endothelium interactions, a hallmark of CV diseases, in rat mesenteric vessels using intravital microscopy and in human arterial cells using a flow chamber system.
RESULTS
Abacavir and didanosine increased rolling, adhesion and emigration in rat vessels. These effects were reversed with antibodies against Macrophage-1 antigen (Mac-1) or intercellular adhesion molecule 1 and were reproduced in human cells. Lamivudine, zidovudine, emtricitabine, and tenofovir had no effects.
CONCLUSIONS
Our results support the association of abacavir and didanosine with CV diseases.
背景
核苷类逆转录酶抑制剂（NRTIs）用于治疗人类免疫缺陷病毒（HIV）感染，但其对心血管系统（CV）的毒性仍存在争议。
方法
我们使用活体显微镜评估了 NRTIs 对大鼠肠系膜血管白细胞-内皮细胞相互作用（CV 疾病的标志）的影响，并使用流动室系统评估了 NRTIs 对人动脉细胞的影响。
结果
阿巴卡韦和去羟肌苷增加了大鼠血管中的滚动、黏附和迁移。这些作用可以被抗巨噬细胞-1 抗原（Mac-1）或细胞间黏附分子 1 的抗体逆转，并且可以在人细胞中重现。拉米夫定、齐多夫定、恩曲他滨和替诺福韦没有这些作用。
结论
我们的结果支持阿巴卡韦和去羟肌苷与 CV 疾病相关联。
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