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PCSK9 mediates the oxidative low‑density lipoprotein‑induced pyroptosis of vascular endothelial cells via the UQCRC1/ROS pathway

  • Authors:
    • Junfa Zeng
    • Jun Tao
    • Linzhen Xi
    • Zuo Wang
    • Lushan Liu
  • View Affiliations / Copyright

    Affiliations: Institute of Cardiovascular Disease, Key Laboratory for Arteriosclerology of Hunan Province, Hunan International Scientific and Technological Cooperation Base of Arteriosclerotic Disease, Hengyang Medical College, University of South China, Hengyang, Hunan 421001, P.R. China
    Copyright: © Zeng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 53
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    Published online on: February 11, 2021
       https://doi.org/10.3892/ijmm.2021.4886
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Abstract

The present study aimed to explore the role and mechanisms of proprotein convertase subtilisin/kexin type 9 (PCSK9) in the oxidized low‑density lipoprotein (oxLDL)‑induced pyroptosis of vascular endothelial cells. For this purpose, human umbilical vein endothelial cells (HUVECs) were incubated with oxLDL (100 µg/ml) for 24 h to induce pyroptosis, which was detected using PI/hoechst33342 double staining. The expression of pyroptosis‑associated molecules was measured by western blot analysis and RT‑qPCR. Reactive oxygen species (ROS) and membrane potential were examined through ROS probe and JC‑1 staining, respectively. PCSK9 and mitochondrial ubiquinol‑cytochrome c reductase core protein 1 (UQCRC1) protein were knocked down by small interfering RNA (siRNA). PCSK9 was overexpressed by lentivirus. The results revealed that oxLDL induced HUVEC injury, pyroptosis and inflammatory factor release, and upregulated the expression of PCSK9 protein in the HUVECs in a concentration‑dependent manner. The silencing of PCSK9 expression with siRNA suppressed the oxLDL‑induced damage to HUVECs, the release of inflammatory substances and the occurrence of pyroptosis. In addition, oxLDL inhibited UQCRC1 expression, promoted mitochondrial membrane potential collapse and damaged mitochondrial function; however, these processes were reversed by the silencing of PCSK9. PCSK9 overexpression induced the pyroptosis of HUVECs, the generation of ROS and the disorder of mitochondrial function by inhibiting UQCRC1. Therefore, PCSK9 mediates the oxLDL‑induced pyroptosis of vascular endothelial cells via the UQCRC1/ROS pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Zeng J, Tao J, Xi L, Wang Z and Liu L: PCSK9 mediates the oxidative low‑density lipoprotein‑induced pyroptosis of vascular endothelial cells via the UQCRC1/ROS pathway. Int J Mol Med 47: 53, 2021.
APA
Zeng, J., Tao, J., Xi, L., Wang, Z., & Liu, L. (2021). PCSK9 mediates the oxidative low‑density lipoprotein‑induced pyroptosis of vascular endothelial cells via the UQCRC1/ROS pathway. International Journal of Molecular Medicine, 47, 53. https://doi.org/10.3892/ijmm.2021.4886
MLA
Zeng, J., Tao, J., Xi, L., Wang, Z., Liu, L."PCSK9 mediates the oxidative low‑density lipoprotein‑induced pyroptosis of vascular endothelial cells via the UQCRC1/ROS pathway". International Journal of Molecular Medicine 47.4 (2021): 53.
Chicago
Zeng, J., Tao, J., Xi, L., Wang, Z., Liu, L."PCSK9 mediates the oxidative low‑density lipoprotein‑induced pyroptosis of vascular endothelial cells via the UQCRC1/ROS pathway". International Journal of Molecular Medicine 47, no. 4 (2021): 53. https://doi.org/10.3892/ijmm.2021.4886
Copy and paste a formatted citation
x
Spandidos Publications style
Zeng J, Tao J, Xi L, Wang Z and Liu L: PCSK9 mediates the oxidative low‑density lipoprotein‑induced pyroptosis of vascular endothelial cells via the UQCRC1/ROS pathway. Int J Mol Med 47: 53, 2021.
APA
Zeng, J., Tao, J., Xi, L., Wang, Z., & Liu, L. (2021). PCSK9 mediates the oxidative low‑density lipoprotein‑induced pyroptosis of vascular endothelial cells via the UQCRC1/ROS pathway. International Journal of Molecular Medicine, 47, 53. https://doi.org/10.3892/ijmm.2021.4886
MLA
Zeng, J., Tao, J., Xi, L., Wang, Z., Liu, L."PCSK9 mediates the oxidative low‑density lipoprotein‑induced pyroptosis of vascular endothelial cells via the UQCRC1/ROS pathway". International Journal of Molecular Medicine 47.4 (2021): 53.
Chicago
Zeng, J., Tao, J., Xi, L., Wang, Z., Liu, L."PCSK9 mediates the oxidative low‑density lipoprotein‑induced pyroptosis of vascular endothelial cells via the UQCRC1/ROS pathway". International Journal of Molecular Medicine 47, no. 4 (2021): 53. https://doi.org/10.3892/ijmm.2021.4886
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