The reverse cholesterol transport mediated by high-density lipoprotein (HDL) is an important mechanism for maintaining body cholesterol, and hence, the crucial anti-atherogenic action of the lipoprotein. Recent studie...The reverse cholesterol transport mediated by high-density lipoprotein (HDL) is an important mechanism for maintaining body cholesterol, and hence, the crucial anti-atherogenic action of the lipoprotein. Recent studies, however, have shown that HDL exerts a variety of anti-inflammatory and anti-atherogenic actions independently of cholesterol metabolism. The present review provides an overview of the roles of sphingosine 1-phosphate (S1P)/S1P receptor and apolipoprotein A-I/scavenger receptor class B type I systems in the anti-atherogenic HDL actions. In addition, the physiological significance of the existence of S1P in the HDL particles is discussed.展开更多
动脉粥样硬化是心血管疾病重要的病理生理基础,延缓和防治动脉粥样硬化对于减少和降低心血管疾病的发病率及病死率具有重要意义。高密度脂蛋白(high density lipoprotein,HDL)通过参与介导胆固醇逆向转运(reverse cholesterol transport...动脉粥样硬化是心血管疾病重要的病理生理基础,延缓和防治动脉粥样硬化对于减少和降低心血管疾病的发病率及病死率具有重要意义。高密度脂蛋白(high density lipoprotein,HDL)通过参与介导胆固醇逆向转运(reverse cholesterol transport,RCT)在抗动脉粥样硬化的形成和进展中发挥了重要作用。Preβ-1高密度脂蛋白(prebeta-1 high density lipoprotein,Preβ-1HDL)作为HDL的一种亚类,是外周细胞移出胆固醇的最初接受体,直接参与了RCT的起始步骤,并在随后的胆固醇酯化及转运中起着重要作用。本文就Preβ-1HDL的结构、代谢及其与心血管疾病的关系作一简要综述。展开更多
Patients with type 2 diabetes mellitus(T2DM) frequently exhibit macrovascular complications of atherosclerotic cardiovascular(CV) disease. High density lipoproteins(HDL) are protective against atherosclerosis. Low lev...Patients with type 2 diabetes mellitus(T2DM) frequently exhibit macrovascular complications of atherosclerotic cardiovascular(CV) disease. High density lipoproteins(HDL) are protective against atherosclerosis. Low levels of HDL cholesterol(HDL-C) independently contribute to CV risk. Patients with T2 DM not only exhibit low HDL-C, but also dysfunctional HDL. Furthermore, low concentration of HDL may increase the risk for the development of T2 DM through a decreased β cell survival and secretory function. In this paper, we discuss emerging concepts in the relationship of T2 DM with HDL.展开更多
This study aimed to examine whether expression of human hepatic lipase（hHL） exerted an intracellular effect on hepatic production of apolipoprotein（apo） A-I.The levels of secreted and cell-associated apoA-I were c...This study aimed to examine whether expression of human hepatic lipase（hHL） exerted an intracellular effect on hepatic production of apolipoprotein（apo） A-I.The levels of secreted and cell-associated apoA-I were contrasted between primary hepatocytes isolated from Lipc-nuW and C57BL/6 mice,and between Lipc-nuW hepatocytes transfected with either hHL-encoding or control adenovirus.An HSPG-binding deficient hHL protein（hHLmt） was used to determine the impact of cell surface binding on HL action.Accumulation of apoA-I in conditioned media of primary hepatocytes isolated from Lipc-nuW mice was increased as compared to that from C57BL/6 mice.Metabolic labeling experiments showed that secretion of ＇＇S-apoA-I from Lipc-nuW cells was significantly higher than that from C57BL/6 cells.Expression of hHL in Lipc-nuW hepatocytes,through adenovirus-mediated gene transfer,resulted in decreased synthesis and secretion of ＇S-apoA-I,but not S-apoE,as compared with cells transfected with control adenovirus.Expression of HSPG-binding deficient hHLmt in Lipc-nuW cells also exerted an inhibitory effect on apoA-I production,even though hHLmt displayed impaired exit from the endoplasmic reticulum as compared with hHL.Subcellular fractionation revealed that expression of hHL or hHLmt led to increased microsome-association of apoA-I relative to non-transfected control.Expression of hHL negatively impacts hepatic production of apoA-I.展开更多
基金Supported by Grants-in-Aid for scientific research from the Japan Society for the Promotion of Science,No.20015008,20054003,and 21390016
文摘The reverse cholesterol transport mediated by high-density lipoprotein (HDL) is an important mechanism for maintaining body cholesterol, and hence, the crucial anti-atherogenic action of the lipoprotein. Recent studies, however, have shown that HDL exerts a variety of anti-inflammatory and anti-atherogenic actions independently of cholesterol metabolism. The present review provides an overview of the roles of sphingosine 1-phosphate (S1P)/S1P receptor and apolipoprotein A-I/scavenger receptor class B type I systems in the anti-atherogenic HDL actions. In addition, the physiological significance of the existence of S1P in the HDL particles is discussed.
文摘动脉粥样硬化是心血管疾病重要的病理生理基础,延缓和防治动脉粥样硬化对于减少和降低心血管疾病的发病率及病死率具有重要意义。高密度脂蛋白(high density lipoprotein,HDL)通过参与介导胆固醇逆向转运(reverse cholesterol transport,RCT)在抗动脉粥样硬化的形成和进展中发挥了重要作用。Preβ-1高密度脂蛋白(prebeta-1 high density lipoprotein,Preβ-1HDL)作为HDL的一种亚类,是外周细胞移出胆固醇的最初接受体,直接参与了RCT的起始步骤,并在随后的胆固醇酯化及转运中起着重要作用。本文就Preβ-1HDL的结构、代谢及其与心血管疾病的关系作一简要综述。
文摘Patients with type 2 diabetes mellitus(T2DM) frequently exhibit macrovascular complications of atherosclerotic cardiovascular(CV) disease. High density lipoproteins(HDL) are protective against atherosclerosis. Low levels of HDL cholesterol(HDL-C) independently contribute to CV risk. Patients with T2 DM not only exhibit low HDL-C, but also dysfunctional HDL. Furthermore, low concentration of HDL may increase the risk for the development of T2 DM through a decreased β cell survival and secretory function. In this paper, we discuss emerging concepts in the relationship of T2 DM with HDL.
基金supported by a grant-in-aid (#T6903) from the Heart and Stroke Foundation of Ontario
文摘This study aimed to examine whether expression of human hepatic lipase（hHL） exerted an intracellular effect on hepatic production of apolipoprotein（apo） A-I.The levels of secreted and cell-associated apoA-I were contrasted between primary hepatocytes isolated from Lipc-nuW and C57BL/6 mice,and between Lipc-nuW hepatocytes transfected with either hHL-encoding or control adenovirus.An HSPG-binding deficient hHL protein（hHLmt） was used to determine the impact of cell surface binding on HL action.Accumulation of apoA-I in conditioned media of primary hepatocytes isolated from Lipc-nuW mice was increased as compared to that from C57BL/6 mice.Metabolic labeling experiments showed that secretion of ＇＇S-apoA-I from Lipc-nuW cells was significantly higher than that from C57BL/6 cells.Expression of hHL in Lipc-nuW hepatocytes,through adenovirus-mediated gene transfer,resulted in decreased synthesis and secretion of ＇S-apoA-I,but not S-apoE,as compared with cells transfected with control adenovirus.Expression of HSPG-binding deficient hHLmt in Lipc-nuW cells also exerted an inhibitory effect on apoA-I production,even though hHLmt displayed impaired exit from the endoplasmic reticulum as compared with hHL.Subcellular fractionation revealed that expression of hHL or hHLmt led to increased microsome-association of apoA-I relative to non-transfected control.Expression of hHL negatively impacts hepatic production of apoA-I.
