Methionine sulfoxide reductase A attenuates atherosclerosis via repairing dysfunctional HDL in scavenger receptor class B type I deficient mice
| Autor: | Jia Cao, Dongfang Wu, Feifei Li, Hong Yu, Binyi Wang, Yanyong Xu, Chenkun Tan, Yiyong Chen, Xiaojie Zhao |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Apolipoprotein E Male medicine.medical_specialty Blotting Western Real-Time Polymerase Chain Reaction Biochemistry 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine High-density lipoprotein Internal medicine Genetics medicine Animals Humans Scavenger receptor Molecular Biology Cholesterol Macrophages Lentivirus Liver X receptor alpha Hep G2 Cells Scavenger Receptors Class B Atherosclerosis Immunohistochemistry Mice Inbred C57BL 030104 developmental biology Endocrinology chemistry Methionine Sulfoxide Reductases LDL receptor lipids (amino acids peptides and proteins) Female Lipoproteins HDL 030217 neurology & neurosurgery Biotechnology MSRA Lipoprotein Plasmids |
| Zdroj: | FASEB journal : official publication of the Federation of American Societies for Experimental BiologyREFERENCES. 34(3) |
| ISSN: | 1530-6860 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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