Methionine sulfoxide reductase A attenuates atherosclerosis via repairing dysfunctional HDL in scavenger receptor class B type I deficient mice.
FASEB J
; 34(3): 3805-3819, 2020 03.
Article
in En
| MEDLINE
| ID: mdl-31975555
ABSTRACT
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 lecithincholesterol 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Atherosclerosis
/
Methionine Sulfoxide Reductases
/
Scavenger Receptors, Class B
/
Lipoproteins, HDL
Limits:
Animals
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Female
/
Humans
/
Male
Language:
En
Journal:
FASEB J
Journal subject:
BIOLOGIA
/
FISIOLOGIA
Year:
2020
Document type:
Article
Affiliation country:
China