MOLECULAR MECHANISM OF ROSIGLITAZONE INHIBITING ATHEROSCLEROSIS IN APOE MICE BY REGULATING ABCA1 REVERSE CHOLESTEROL TRANSPORT

Yu Zhang^{1, #, *}, Fuzhong Liu^{2, #}, Lingjun Zhu¹, Jian Ye¹

¹Department of Cardiology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou 310000, Zhejiang Province, China - ²Department of Cardiology, Jiashan People's Hospital, Jiaxing 314000, Zhejiang Province, China

Objective: To analyze the molecular mechanism of rosiglitazone inhibiting atherosclerosis in ApoE mice by regulating adenosine triphosphate-binding cassette transporter A1 (ABCA1). 

Methods: Twenty ApoE knockout mice were divided into a model group (high-fat diet + normal saline gavage) and a rosiglitazone group (high-fat diet + 0.5mg/kg/d rosiglitazone + normal saline), whilst 10 normal healthy mice were given a normal diet. Blood lipid levels, arterial wall thickness, and liver and aortic pathology were observed. Scavenger receptor BI (SR-B1) and ABCA1 protein expressions were detected by Western blot analysis. 

Results: The levels of TC, TG, LDL-C, and HDL-C in the model group were significantly higher than those in the normal control group (P<0.01), while the levels of TC, TG, and LDL-C in the rosiglitazone group were significantly lower than those in the model group, and the HDL-C level was significantly higher than that in the model group (P<0.01). The thicknesses of the proximal and distal artery walls of the rosiglitazone group were smaller than those of the model group, and this difference was statistically significant (P<0.01). In the model group, the structure of the hepatic lobule was not obvious, and the hepatocytes were obviously swollen or expanded. Oil red O staining showed a large number of lipid droplets in the liver cells. The morphology of the hepatocytes in the rosiglitazone group was better than that in the model group, and small lipid droplets were also observed. In the model group, there were obvious atherosclerotic plaques in the aorta, which were bright red after staining and protruded to the lumen, leading to a decrease in lumen size. The area of the aorta staining was significantly reduced in the rosiglitazone group, that is, there was a decrease in plaque. The protein expressions of SR-B1 and ABCA1 in the liver for mice in the model group was significantly lower than that in the normal control group (P<0.05), while that in the rosiglitazone group was significantly higher than that in the model group (P<0.05). 

Conclusion: Rosiglitazone can regulate blood lipid metabolism and reduce liver lipid deposition in atherosclerotic mice. The mechanism may be related to the regulation of SR-B1 and ABCA1 expression and reverse cholesterol transport.