The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that aff...The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein(LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X(Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers- such as cholesterol precursor sterols, plant sterols, and cholestanol- may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation.展开更多
法尼醋X受体(farnesoid x receptor,FXR)属于配体依赖的核转录因子,FXR主要在肝脏、肠道、肾脏、肾上腺等表达,FXR因其可被内源性配体胆汁酸激活,故又称胆汁酸受体,他是孤儿核受体超家族中的一员.被内源性配体胆汁酸激活后的FXR在甘油三...法尼醋X受体(farnesoid x receptor,FXR)属于配体依赖的核转录因子,FXR主要在肝脏、肠道、肾脏、肾上腺等表达,FXR因其可被内源性配体胆汁酸激活,故又称胆汁酸受体,他是孤儿核受体超家族中的一员.被内源性配体胆汁酸激活后的FXR在甘油三酯(triglyceride,TG)代谢过程中起着重要作用,FXR可通过调控与TG代谢的关键酶、脂蛋白和相应受体,从而使肝脏及循环血液中TG含量达到稳态平衡,本文就FXR对TG的代谢调节作一综述.展开更多
肝脏的低密度脂蛋白受体(LDLR)是清除血浆低密度脂蛋白(LDL)的主要途径,并且是一个非常重要的心血管系统疾病的治疗靶点。LDLR的表达量受到转录和转录后两方面的调控。这里介绍一种新近发现的、通过泛素化作用经转录后途径调控LDLR的蛋...肝脏的低密度脂蛋白受体(LDLR)是清除血浆低密度脂蛋白(LDL)的主要途径,并且是一个非常重要的心血管系统疾病的治疗靶点。LDLR的表达量受到转录和转录后两方面的调控。这里介绍一种新近发现的、通过泛素化作用经转录后途径调控LDLR的蛋白Idol(inducible degrader of the LDLR)。Idol是一个肝脏X受体(LXR)的靶分子,具有E3泛素连接酶活性,可以介导LDLR的泛素化,并在溶酶体降解。Idol还有另外两个LDLR家族的靶蛋白VLDLR和ApoER2。尽管Idol和前蛋白转化酶枯草溶菌素9(PCSK9)存在着很多相似之处,但它们在调控LDLR的途径上是不同的。最近的工作显示Idol与人类的LDL水平有关,Idol可能在人类的血脂代谢有重要作用。展开更多
法尼酯X受体(Farnesoid X Receptor,FXR)属于配体依赖的核转录因子,可被内源性配体胆汁酸激活,通过调节胆汁酸、胆固醇、脂蛋白及脂肪酸代谢维持血浆中脂质的稳态,从而达到调节脂质代谢的目的。最近研究发现FXR在脉管系统中也有表达活性...法尼酯X受体(Farnesoid X Receptor,FXR)属于配体依赖的核转录因子,可被内源性配体胆汁酸激活,通过调节胆汁酸、胆固醇、脂蛋白及脂肪酸代谢维持血浆中脂质的稳态,从而达到调节脂质代谢的目的。最近研究发现FXR在脉管系统中也有表达活性,开辟了FXR调节脂质代谢的新途径。随着新配体及靶基因的发现,研究FXR的作用机制以及寻找对脂质代谢具有调控作用的FXR的配体,对于脂代谢异常和动脉粥样硬化的防治具有重要意义。本文综述了该领域的最新进展。展开更多
脂蛋白(a)[Lp(a)]是由载脂蛋白(a)(apo(a))与载脂蛋白B100(apoB100)通过共价键连接的脂蛋白。高血浆水平Lp(a)是心血管疾病的独立风险因子,Lp(a)的血浆水平主要受遗传因素调控,主要有LPA[lipoprotein,Lp(a)]基因的三环结构域kringle IV/...脂蛋白(a)[Lp(a)]是由载脂蛋白(a)(apo(a))与载脂蛋白B100(apoB100)通过共价键连接的脂蛋白。高血浆水平Lp(a)是心血管疾病的独立风险因子,Lp(a)的血浆水平主要受遗传因素调控,主要有LPA[lipoprotein,Lp(a)]基因的三环结构域kringle IV/2拷贝数和单核苷酸多态性(SNP)。欧洲动脉粥样硬化协会(EAS)和美国心脏病协会(AHA)建议对于高Lp(a)的人群应当考虑降高Lp(a)的治疗。目前已有多种降高Lp(a)的药物和方法,如血浆分离置换法、雌激素治疗、反义核苷酸治疗、类法尼醇X核内受体(farnesoid X receptor,FXR)激动治疗等,但应用于临床的降高Lp(a)的药物和方法依然缺乏。本文拟就降Lp(a)的药物和方法进展情况进行综述。展开更多
文摘目的探讨脂蛋白酯酶在compound K调节血脂水平中的作用。方法 36只雄性SD大鼠随机分为6组,除对照组外均给予高脂饮食,对照组和模型组给予生理盐水腹腔注射,compound K给药组分别给予compound K 1、3、9 mg/kg腹腔注射,GGPP组同时给予compound K 3、9 mg/kg GGPP。4周后处死动物,取样测定血脂、肝素后脂蛋白酯酶活性、脂蛋白酯酶表达水平等;培养大鼠肝细胞株BRL,分别给予compound K 3、10、30μmol/L处理12 h后,检测脂蛋白酯酶表达水平。结果与模型组比较,compound K 3、9 mg/kg组的总胆固醇、低密度脂蛋白胆固醇、三酰甘油显著降低,高密度脂蛋白胆固醇、肝素后血清脂蛋白酯酶活性和脂蛋白酯酶表达量显著增高,差异有统计学意义(P<0.05),且呈剂量依赖性。体外细胞试验结果与动物实验一致。结论 compound K能够通过增加脂蛋白酯酶的表达和活性达到降低高脂饮食大鼠血清三酰甘油的作用,其机制与compound K激活肝X受体α相关。
文摘The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein(LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X(Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers- such as cholesterol precursor sterols, plant sterols, and cholestanol- may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation.
文摘法尼醋X受体(farnesoid x receptor,FXR)属于配体依赖的核转录因子,FXR主要在肝脏、肠道、肾脏、肾上腺等表达,FXR因其可被内源性配体胆汁酸激活,故又称胆汁酸受体,他是孤儿核受体超家族中的一员.被内源性配体胆汁酸激活后的FXR在甘油三酯(triglyceride,TG)代谢过程中起着重要作用,FXR可通过调控与TG代谢的关键酶、脂蛋白和相应受体,从而使肝脏及循环血液中TG含量达到稳态平衡,本文就FXR对TG的代谢调节作一综述.
文摘肝脏的低密度脂蛋白受体(LDLR)是清除血浆低密度脂蛋白(LDL)的主要途径,并且是一个非常重要的心血管系统疾病的治疗靶点。LDLR的表达量受到转录和转录后两方面的调控。这里介绍一种新近发现的、通过泛素化作用经转录后途径调控LDLR的蛋白Idol(inducible degrader of the LDLR)。Idol是一个肝脏X受体(LXR)的靶分子,具有E3泛素连接酶活性,可以介导LDLR的泛素化,并在溶酶体降解。Idol还有另外两个LDLR家族的靶蛋白VLDLR和ApoER2。尽管Idol和前蛋白转化酶枯草溶菌素9(PCSK9)存在着很多相似之处,但它们在调控LDLR的途径上是不同的。最近的工作显示Idol与人类的LDL水平有关,Idol可能在人类的血脂代谢有重要作用。
文摘法尼酯X受体(Farnesoid X Receptor,FXR)属于配体依赖的核转录因子,可被内源性配体胆汁酸激活,通过调节胆汁酸、胆固醇、脂蛋白及脂肪酸代谢维持血浆中脂质的稳态,从而达到调节脂质代谢的目的。最近研究发现FXR在脉管系统中也有表达活性,开辟了FXR调节脂质代谢的新途径。随着新配体及靶基因的发现,研究FXR的作用机制以及寻找对脂质代谢具有调控作用的FXR的配体,对于脂代谢异常和动脉粥样硬化的防治具有重要意义。本文综述了该领域的最新进展。
文摘脂蛋白(a)[Lp(a)]是由载脂蛋白(a)(apo(a))与载脂蛋白B100(apoB100)通过共价键连接的脂蛋白。高血浆水平Lp(a)是心血管疾病的独立风险因子,Lp(a)的血浆水平主要受遗传因素调控,主要有LPA[lipoprotein,Lp(a)]基因的三环结构域kringle IV/2拷贝数和单核苷酸多态性(SNP)。欧洲动脉粥样硬化协会(EAS)和美国心脏病协会(AHA)建议对于高Lp(a)的人群应当考虑降高Lp(a)的治疗。目前已有多种降高Lp(a)的药物和方法,如血浆分离置换法、雌激素治疗、反义核苷酸治疗、类法尼醇X核内受体(farnesoid X receptor,FXR)激动治疗等,但应用于临床的降高Lp(a)的药物和方法依然缺乏。本文拟就降Lp(a)的药物和方法进展情况进行综述。
