Zhou, BodaZu, LingyunChen, YongZheng, XilongWang, YuhuiPan, BingDong, MinZhou, EnchenZhao, MingmingZhang, YouyiZheng, LeminGao, Wei2018-09-262018-09-262017-01-10Lipids in Health and Disease. 2017 Jan 10;16(1):3http://hdl.handle.net/1880/10796310.11575/PRISM/44990Abstract 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 (NO2-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.Journal Article2018-09-26enThe Author(s).https://doi.org/10.1186/s12944-016-0388-z