Statins Combined with AAV8-TBG-LOX-1 Reduce the Vascular Lipid-driven Inflammatory Response and Inhibit Atherosclerosis

作     者：Wen-ping ZHOU Xin-rui FAN Song-hai LI Zhuang-lin ZENG Yu-miao WEI Wen-ping ZHOU;Xin-rui FAN;Song-hai LI;Zhuang-lin ZENG;Yu-miao WEI

作者机构：Department of CardiologyThe Central Hospital of WuhanTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430014China Key Laboratory for Molecular Diagnosis of Hubei ProvinceThe Central Hospital of WuhanTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430014China Sleep and Neuro Imaging CenterFaculty of PsychologySouthwest UniversityChongqing 400715China Department of CardiologyWuhan Fourth HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430033China Department of Emergency MedicineUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Department of CardiologyUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Hubei Key Laboratory of Biological Targeted TherapyUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Hubei Engineering Research Center for Immunological Diagnosis and Therapy of Cardiovascular DiseasesUnion HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China 

出 版 物：《当代医学科学（英文）》 (Current Medical Science)

年 卷 期：2024年第44卷第6期

页      面：1097-1102页

核心收录：

基　　金：National Natural Science Foundation of China, NSFC, (81873491) National Natural Science Foundation of China, NSFC Natural Science Foundation of Yunnan Province, (WX20C06) Natural Science Foundation of Yunnan Province 

主　　题：atherosclerosis oxidized low-density lipoprotein statin adeno-associated virus AAV8-TBG-LOX-1 

摘      要：Objective:Imbalances in liver lipid metabolism and inflammatory reactions driven by oxidized lipid deposition in blood vessels constitute the core of *** degradation of cholesterol in the liver promotes oxidative modification of lipid particles and their deposition on the blood vessel wall in the peripheral *** blood vessel wall engulfs and processes oxidized low-density lipoprotein(Ox-LDL)as foreign matter through pattern recognition receptors,ultimately forming lipid-encapsulated *** them,endothelial cell oxidized low density lipoprotein receptor 1(LOX1)phagocytosis is an important link in initiating and promoting this mechanism,and hepatocytes,which are the core of lipid metabolism,are unable to process oxidized lipid particles because of the lack of receptors for the uptake of *** objective of this study was to investigate whether continuous clearance of Ox-LDL through the liver metabolic pathway could provide better protection against statins ***:This study used statins combined with an adeno-associated virus(AAV8-TBG-LOX-1)liver-specific transfection system developed by our research group,in which statins reduced the level of LDL and promoted the ectopic expression of LOX-1 in hepatocytes to clear the continuous production of *** ApoE knockout mouse model was used to study the effects of virus transfection and liver uptake and degradation of *** confocal detection,Oil red staining and immunofluorescence staining were used to observe the effects of combined therapy on anti-atherosclerotic ***:Laser confocal microscopy revealed that the recombinant viral vector AAV8-TBG-LOX-1 could specifically transfect hepatocytes and express LOX-1,which mediate hepatocyte phagocytosis and clearance of *** red O staining of the aorta and valvular ring suggested that statins combined with AAV8-TBG-LOX-1 significantly inhibited atherosclerotic *** immunofluorescence sta