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Methionine sulfoxide reductase A attenuates atherosclerosis via repairing dysfunctional HDL in scavenger receptor class B type I deficient mice
Author(s) -
Xu Yanyong,
Li Feifei,
Zhao Xiaojie,
Tan Chenkun,
Wang Binyi,
Chen Yiyong,
Cao Jia,
Wu Dongfang,
Yu Hong
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201902429r
Subject(s) - msra , scavenger receptor , medicine , endocrinology , apolipoprotein b , high density lipoprotein , cholesterol , liver x receptor alpha , inflammation , lipoprotein , chemistry , reverse cholesterol transport , apolipoprotein e , methionine , biology , biochemistry , nuclear receptor , disease , amino acid , gene , transcription factor
High‐density lipoprotein (HDL), a well‐known atheroprotective factor, can be converted to proatherogenic particles in chronic inflammation. HDL‐targeted therapeutic strategy for atherosclerotic cardiovascular disease (CVD) is currently under development. This study aims to assess the role of methionine sulfoxide reductase A (MsrA) in abnormal HDL and its related disorders in scavenger receptor class B type I deficient ( SR‐BI −/− ) mice. First, we demonstrated that MsrA overexpression attenuated ROS level and inflammation in HepG2 cells. For the in vivo study, SR‐BI −/− mice were intravenously injected with lentivirus to achieve hepatic MsrA overexpression. High‐level hepatic MsrA significantly reduced the plasma free cholesterol contents, improved HDL functional proteins apolipoprotein A‐I (apoAI), apoE, paraoxonase1 (PON1), and lecithin:cholesterol acyltransferase (LCAT), while decreased the pro‐inflammatory property of dysfunctional HDL, contributing to reduced atherosclerosis and hepatic steatosis in Western diet‐fed mice. Furthermore, the study revealed that hepatic MsrA altered the expression of several genes controlling HDL biogenesis, cholesterol esterification, cholesterol uptake mediated by low‐density lipoprotein receptor (LDLR) and biliary excretion, as well as suppressed nuclear factor κB (NF‐κB) signaling pathway, which largely relied on liver X receptor alpha (LXRα)‐upregulation. These results provide original evidence that MsrA may be a promising target for the therapy of dysfunctional HDL‐related CVD.