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Objective:To explore the pathogenesis of gallbladder cholesteryl polyps (GCP) and gallbladder cholesterol calculus (GCC) by studying the different changes of mucin (MUC) expression and reverse cholesterol transporter (RCT) in gallbladder mucosa epithelium.Methods:The data of 10 GCP patients (GCP group), 10 GCC patients (GCC group) and 5 patients with normal gallbladder resection (control group) were retrospectively analyzed, who underwent cholecystectomy in the Department of General Surgery, Xuanwu Hospital, Capital Medical University from January to December 2021. Among the 10 patients in the GCP group, there were 5 males and 5 females, aged (43.40±9.59) years old. Among the 10 patients in the GCC group, 5 males and 5 female, aged (45.00±8.13) years old. Among the 5 patients in the control group, there were 3 males and 2 females, aged (43.80±6.01) years old. Immunohistochemical analysis was used to investigate the expression differences of various subtypes of MUC and RCT [ATP binding cassette transporter G1 (ABCG1) and B group type I scavenger receptor (SR-BI)] among each group.Results:Compared with the control group, the expression of MUC1 (3.40±0.70 vs. 0), MUC5AC (1.50±0.53 vs. 0), MUC6 (4.70±0.48 vs. 0), and ABCG1 (3.50±0.53 vs. 1.60±0.55) in the gallbladder mucosa of the GCP group increased, while the expression score of SR-BI decreased (1.70±0.48 vs. 3.40±0.55), with statistical significance (all P<0.001). Compared with the control group, the expression of MUC1 (4.80±0.42 vs. 0), MUC5AC (4.70±0.48 vs. 0), MUC6 (3.30±0.67 vs. 0), and ABCG1 (3.40±0.52 vs. 1.60±0.55) in the gallbladder mucosa of the GCC group increased, while the expression score of SR-BI decreased (0 vs. 3.40±0.55), with statistically significant differences (all P<0.001). Conclusion:The different expression levels of MUC1, MUC5AC, MUC6, and RCT proteins lead to the differential formation of GCP and GCC on the basis of the co-pathogenesis in high cholesterol in bile.
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Aim To investigate the molecular mechanism of metformin inhibiting atherosclerosis in ApoE 1_ mice by reverse cholesterol transport. Methods Eighteen ApoE -/ _ mice were randomly divided into three groups, control group, model group and metformin group, and body weight changes were monitored weekly. Blood samples were taken to measure serum lipid levels; animal ultrasound was used to measure abdominal aortic wall thickness; HE and oil red 0 staining were used to evaluate the degree of liver steatosis; Western blot was used to detect the expression of liver cholesterol reverse transport-related proteins LXRa and ABCA1. Results Compared with control group, the body weight, serum T C, T G, and LDL in model group increased, HDL decreased(P <0. 05), abdominal aortic wall thickened (P <0. 05), liver fat deposition increased, and L X R a, ABCA1 expression was reduced. In metformin group, body weight, serum T C, T G, LDL decreased, HDL increased (P <0. 05), liver fat deposition and abdominal aortic wall thickness were significandy reduced (P <0. 05), and LXRa and ABCA1 expressions markedly increased (P <0. 0 5). Conclusions Metformin can delay the progression of atherosclerosis by up-regulating the expression of liver cholesterol reverse transport related proteins LXRa and ABCA1, enhancing liver reverse cholesterol transport, regulating blood lipid metabolism and reducing liver lipid deposition.
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AIM:To study whether homocysteine (Hcy) inhibits the expression of ATP-binding cassette transporter A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1) by microRNA-33 (miRNA-33) signaling, and reduces the efficiency of reverse cholesterol transport (RCT).METHODS:RAW264.7 macrophages were induced by oxidized low-density lipoprotein (ox-LDL) to establish foam cell model.Oil red O staining was used to determine whether the model was established successfully.miRNA-33 mimics and miRNA-33 inhibitor were transfected into the cells by Lipofectamine 2000, and the cells were exposed to Hcy at concentration of 5 mmol/L for 24 h.The intracellular lipid droplets were observed by Oil red O staining.The expression of ABCA1 and ABCG1 at mRNA and protein levels was determined by real-time PCR and Western blot.The cellular cholesterol content was analyzed by HPLC, and effluent rate of cholesterol was detected by the method of liquid scintillation counting.RESULTS:Compared with blank control group, the lipid content in miRNA-33 mimics group was increased, and the expression of ABCA1 and ABCG1 at mRNA and protein levels was decreased (P<0.05).The intracellular cholesterol content was increased gradually (P<0.05) , and the cellular cholesterol efflux rate was gradually decreased (P<0.05) in miRNA-33 mimics group.Compared with blank control group, the testing results in miRNA-33 inhibitor group were the opposition of those in miRNA-33 mimics group (P<0.05).No difference of the above indexes among blank control group, miRNA-33 mimics-NC group and miRNA-33 inhibitor-NC group was observed.CONCLUSION:Hcy inhibits the mRNA and protein expression of ABCA1 and ABCG1 through miRNA-33 signaling, and reduces the efficiency of RCT in RAW264.7 macrophage-derived foam cells.
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ABSTRACT Atherosclerosis (AS) is the principle cause of cardiovascular disease. For many years, AS was regarded as irreversible. However, recent accumulated evidence suggests that AS can regress with proper manipulation. Studies from animal models show that low cholesterol diet can induce obvious regression of AS plaques; Drugs, such as probucol, clolestyramine, lovastatin, isradipine, fosinopril, etc, can reverse the AS respectively by manipulating plasma lipoprotein, scavenging free radicals, blocking calcium channel or inhibiting an-giotensin converting enzyme. Clinical trials furthersubstantiate that good lifestyle and effective control of plasma lipoprotein can reduce clinical events and cause AS plaques regression. Although, AS plaques can regress is no longer in doubt, the mechanism is still unknown. The HDL-mediated reverse cholesterol transport system, apoptosis of the plaque cells may play an important role.