High-density lipoprotein and atherosclerosis: Roles of lipid transporters

Various previous studies have found a negative cor-relation between the risk of cardiovascular events and serum high-density lipoprotein(HDL) cholesterol levels. The reverse cholesterol transport, a pathway of choles-terol from peripheral tissue to liver which has several potent antiatherogenic properties. For instance, the particles of HDL mediate to transport cholesterol from cells in arterial tissues, particularly from atherosclerotic plaques, to the liver. Both ATP-binding cassette trans-porters(ABC) A1 and ABCG1 are membrane cholesterol transporters and have been implicated in mediating cholesterol effluxes from cells in the presence of HDL and apolipoprotein A-I, a major protein constituent of HDL. Previous studies demonstrated that ABCA1 and ABCG1 or the interaction between ABCA1 and ABCG1 exerted antiatherosclerotic effects. As a therapeutic approach for increasing HDL cholesterol levels, much focus has been placed on increasing HDL cholesterol levels as well as enhancing HDL biochemical functions. HDL therapies that use injections of reconstituted HDL, apoA-I mimetics, or full-length apoA-I have shown dramatic effectiveness. In particular, a novel apoA-I mi-metic peptide, Fukuoka University ApoA-I Mimetic Pep-tide, effectively removes cholesterol via specific ABCA1 and other transporters, such as ABCG1, and has an an-tiatherosclerotic effect by enhancing the biological func-tions of HDL without changing circulating HDL choles-terol levels. Thus, HDL-targeting therapy has significant atheroprotective potential, as it uses lipid transporter-targeting agents, and may prove to be a therapeutic tool for atherosclerotic cardiovascular diseases.

Overexpression of the steroidogenic acute regulatory protein increases the expression of ATP-binding cassette transporters in microvascular endothelial cells(bEnd.3)

Objective:To determine the effect of steroidogenic acute regulatory protein(StAR) overexpression on the levels of adenosine triphosphate(ATP)-binding cassette transporter A1(ABCA1) and ATP-binding cassette transporter G1(ABCG1) in an endothelial cell line(bEnd.3).Methods:The StAR gene was induced in bEnd.3 cells with adenovirus infection.The infection efficiency was detected by fluorescence activated cell sorter(FACS) and fluorescence microscopy.The expressions of StAR gene and protein levels were detected by real-time polymerase chain reaction(PCR) and Western blot.The gene and protein levels of ABCA1 and ABCG1 were detected by real-time PCR and Western blot after StAR overexpression.Results:The result shows that StAR was successfully overexpressed in bEnd.3 cells by adenovirus infection.The mRNA and protein expressions of ABCA1 and ABCG1 were greatly increased by StAR overexpression in bEnd.3 cells.Conclusion:Overexpression of StAR increases ABCA1 and ABCG1 expressions in endothelial cells.

High nuclear ABCG1 expression is a poor predictor for hepatocellular carcinoma patient survival

Background:ATP-binding cassette transporter G1(ABCG1)regulates cellular cholesterol homeostasis and plays a significant role in tumor immunity.But,for hepatocellular carcinoma(HCC),the role of ABCG1 has not been investigated.Thus,the aim of this study was to evaluate the prognostic value and clinicopathological significance of ABCG1 in HCC.Methods:One hundred and four adult patients with HCC were enrolled,and ABCG1 expression in paired HCC specimens was determined by immunohistochemistry.All these patients were stratified by ABCG1 expression,Kaplan-Meier analysis was used to compare the overall survival(OS)and recurrence-free survival(RFS),and Cox regression analysis was used to determine independent predictors of tumor recurrence.Results:Upregulation of ABCG1 was observed in HCC samples compared to matched tumor-adjacent tissues.Patients with high nuclear ABCG1 expression had lower OS and RFS(P=0.012 and P=0.020,respectively).High nuclear ABCG1 expression was related to larger tumor size(P=0.004)and tumor recurrence(P=0.027).Although ABCG1 was expressed in the cytoplasm,cytosolic expression could not predict the outcome in patients with HCC.A new stratification pattern was established based on the heterogenous ABCG1 expression pattern:high risk(High^(nucleus)/Low^(cytosol)),moderate risk(High^(nucleus)/High^(cytosol) or Low^(nucleus)/Low^(cytosol)),and low risk(Low^(nucleus)/High^(cytosol)).This ABCG1-based risk stratification could distinguish the different OS and RFS in patients with HCC.Multivariate Cox regression analysis indicated that ABCG1 high risk was an independent predictor of poor RFS(P=0.015).Conclusions:High nuclear ABCG1 expression indicates poor prognosis in patients with HCC.Asymmetric distribution of ABCG1 in the nucleus and cytoplasm may have an important role in tumor recurrence.

骨桥蛋白对小鼠胆囊结石形成的作用及其机制探讨

目的研究骨桥蛋白(OPN)基因敲除对小鼠胆囊结石形成的影响及其作用机制。方法选取7只OPN基因敲除小鼠和7只C57BL/6J普通小鼠致石饮食喂养8周,分别作为敲除组和对照组。观察两组小鼠胆结石形成率,检测胆汁胆固醇含量、ATP结合盒转运子G亚家族成员5(ABCG5)、ABCG8 mRNA和蛋白在胆囊组织中的表达。结果敲除组小鼠结石形成率(14.29%)低于对照组(85.71%)(P<0.05)。敲除组小鼠胆汁胆固醇含量(5.35±1.08)低于对照组(9.34+0.85)(P<0.05)。敲除组小鼠ABCG5、ABCG8 mRNA和蛋白表达水平低于对照组(P <0.05)。结论 OPN基因敲除小鼠胆结石形成率较普通小鼠低,可能与OPN敲除后胆囊胆固醇转运蛋白ABCG5、ABCG8表达受抑制,导致胆囊胆汁中胆固醇含量降低有关。