阿托伐他汀对Ox-LDL/β2GPⅠ/anti-β2GPⅠ诱导的血管内皮功能紊乱的改善作用及其机制

doi:10.13481/j.1671-587X.20220207

Abstract

Abstract: Objective

To investigate the effect of atorvastatin（ATO） on the vascular endothelial cell injury induced by oxidized low-density lipoprotein （Ox-LDL） /β2-glycoprotein Ⅰ （β2GPⅠ）/anti-β2-glycoprotein Ⅰ antibody （anti-β2GPⅠ） complex and its effect on the TRAF3 interacting protein 2 （TRAF3IP2）/ Ⅰ kappa B kinase （IKKγ）/ nuclear factor kappa-B （NF-κB） signaling pathway， and to elucidate the possible molecular mechanism of improvement effect of ATO on the endothelial cell injury in the context of antiphospholipid syndrome （APS）.

Methods

The endothelial cell injury models were established by treating the human umbilical vein endothelial cells （HUVECs） with β2GPⅠ（100 mg·L^―1），Ox-LDL（50 mg·L^―1），β2GPⅠ/anti-β2GPⅠ（100 mg·L^―1），Ox-LDL/β2GPⅠ and Ox-LDL/β2GPⅠ/anti-β2GPⅠ complex.The HUVECs were divided into control group，β2GPⅠ group，Ox-LDL group，β2GPⅠ/anti-β2GPⅠ group，Ox-LDL/β2GPⅠ group，Ox-LDL/β2GPⅠ/anti-β2GPⅠ group，ATO（10 μmol·L^―1）+ Ox-LDL/β2GPⅠ group and ATO+ Ox-LDL/β2GPⅠ/anti-β2GPⅠ group. The survival rates of HUVECs in various groups were detected by MTT assay， the fluorescence intensities of intracellular reactive oxygen species （ROS） in various groups were detected by chemical fluorescence probe， and the endothelin-1（ET-1） levels in various groups were detected by ELISA. The expression levels of TRAF3IP2， p-IKKγ and p-NF-κB p65 in the HUVECs in various groups were detected by Western blotting method.

Results

Compared with control group， the survival rates of HUVECs in Ox-LDL/β2GPⅠ group and Ox-LDL/β2GPⅠ/anti-β2GPⅠ group were significantly decreased （P<0.01）；compared with Ox-LDL/β2GPⅠ group and Ox-LDL/β2GPⅠ/anti-β2GPⅠ group，after treatment for 1 h，the survival rates in ATO+Ox-LDL/β2GPⅠ group and ATO+Ox-LDL/β2GPⅠ/anti-β2GPⅠ group were significantly increased （P<0.05）. Compared with control group， the fluorescence intensities of ROS and the levels of ET-1 in the HUVECs in Ox-LDL/β2GPⅠ group and Ox-LDL/β2GPⅠ/anti-β2GPⅠ group were significantly increased （P<0.01）； the expression levels of TRAF3IP2， p-IKKγ and p-NF-κB P65 proteins in the HUVECs in were significantly increased （P<0.05）. Compared with Ox-LDL/β2GPⅠ group and Ox-LDL/β2GPⅠ/anti-β2GPⅠ group，the fluorescence intensties of ROS and the levels of ET-1， and the expression levels of TRAF3IP2， p-IKKγ and p-NF-κB P65 in ATO+Ox-LDL/β2GPⅠ group and ATO Ox-LDL/β2GPⅠ/anti-β2GPⅠ group were significantly decreased （P<0.05）.

Conclusion

ATO could alleviate the vascular endothelial dysfunction induced by Ox-LDL/β2GPⅠ/anti-β2GPⅠ complex，and its mechanism may be related to down-regulating the TRAF3IP2/IKK/NF-κB signaling pathway.

Key words: Endothelial dysfunction, Oxidized low-density lipoprotein, β2-glycoprotein Ⅰ, anti-β2-glycoprotein Ⅰ antibody, Reactive oxygen species, TRAF3 interacting protein 2, Nuclear factor kappa-B

CLC Number:

R543.5

Yinong LIU,Qiang ZHANG,Li XU. Improvement effect of atorvastatin on vascular endothelial dysfunction induced by Ox-LDL/β2GPⅠ/anti-β2GPⅠ complex and its mechanism[J].Journal of Jilin University(Medicine Edition), 2022, 48(2): 317-323.

Figures/Tables 4

References 21

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Improvement effect of atorvastatin on vascular endothelial dysfunction induced by Ox-LDL/β2GPⅠ/anti-β2GPⅠ complex and its mechanism

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