1. Myeloperoxidase-oxidized high density lipoprotein impairs atherosclerotic plaque stability by inhibiting smooth muscle cell migration.
- Author
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Boda Zhou, Lingyun Zu, Yong Chen, Xilong Zheng, Yuhui Wang, Bing Pan, Min Dong, Enchen Zhou, Mingming Zhao, Youyi Zhang, Lemin Zheng, and Wei Gao
- Subjects
ATHEROSCLEROTIC plaque ,CARDIOVASCULAR agents ,MYELOPEROXIDASE ,HIGH density lipoproteins ,CELL migration ,MUSCLE cells ,THERAPEUTICS - Abstract
Background: High density lipoprotein (HDL) has been proved to be a protective factor for coronary heart disease. Notably, HDL in atherosclerotic plaques can be nitrated (NO
2 -oxHDL) and chlorinated (Cl-oxHDL) by myeloperoxidase (MPO), likely compromising its cardiovascular protective effects. Method: Here we determined the effects of NO2 -oxHDL and Cl-oxHDL on SMC migration using wound healing and transwell assays, proliferation using MTT and BrdU assays, and apoptosis using Annexin-V assay in vitro, as well as on atherosclerotic plaque stability in vivo using a coratid artery collar implantation mice model. Results: Our results showed that native HDL promoted SMC proliferation and migration, whereas NO2 -oxHDL and Cl-oxHDL inhibited SMC migration and reduced capacity of stimulating SMC proliferation as well as migration, respectively. OxHDL had no significant influence on SMC apoptosis. In addition, we found that ERK1/2-phosphorylation was significantly lower when SMCs were incubated with NO2 -oxHDL and Cl-oxHDL. Furthermore, transwell experiments showed that differences between native HDL, NO2 -oxHDL and Cl-oxHDL was abolished after PD98059 (MAPK kinase inhibitor) treatment. In aortic SMCs from scavenger receptor BI (SR-BI) deficient mice, differences between migration of native HDL, NO2 -oxHDL and Cl-oxHDL treated SMCs vanished, indicating SR-BI's possible role in HDL-associated SMC migration. Importantly, NO2 -oxHDL and Cl-oxHDL induced neointima formation and reduced SMC positive staining cells in atherosclerotic plaque, resulting in elevated vulnerable index of atherosclerotic plaque. Conclusion: These findings implicate MPO-catalyzed oxidization of HDL may contribute to atherosclerotic plaque instability by inhibiting SMC proliferation and migration through MAPK-ERK pathway which was dependent on SR-BI. [ABSTRACT FROM AUTHOR]- Published
- 2017
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