Low-density lipoprotein receptor (LDLR) and metabolic syndrome (MS) are closely correlated. Changes in LDLR expression, feedback regulation and degradation, impacts of LDLR deficiency on blood lipid levels, roles of LDLR in islet β cell dysfunction and cholesterol homeostasis dysregulation, expression of LDLR gene nuclear transcription factors and polymorphism of LDLR gene segments are all involved in the development of specific components of MS. In recent years, a variety of targets and intervention mechanisms in relation to LDLR and MS have been extensively studied. Knowledge about association between LDLR and MS may contribute to the development of strategies for prevention and treatment of MS. This article reviews the update on the association between LDLR and MS.
Homeostasis ; Humans ; Lipid Metabolism ; Lipoproteins, LDL ; Metabolic Syndrome ; Receptors, LDL

OBJECTIVETo investigate effects of serum HDL(1) on the formation of foam cells from human peripheral blood monocyte-derived macrophages.

METHODSSectie density polyacrylamide gel electrophoresis (sd-PAGE) was applied for isolation and preparation of HDL(1) simultaneously. Monocytes were isolated from human peripheral blood by Ficoll-Hypaque density gradient centrifugation and plastic adsorptive process. The isolated monocytes were stimulated by phorbol 12-myristate 13-acetate (PMA) at a concentration of 50 nmol/L for 48 h and transferred to macrophages. The monocyte-derived macrophages were then coincubated with 80 mg/L ox-LDL and HDL(1) (0, 0.1, 1.0 and 10.0 mg/L) for 6, 12 and 24 h, respectively. The formation of foam cells was identified by transmission electron microscope (TEM), total cholesterol (TC), free cholesterol (FC) and protein (Pro) in cultured cells were quantitatively analyzed by high performance chromatography (HPLC) and modified lowry protein assay, respectively.

RESULTSHDL(1) isolated from human serum by sd-PAGE could significantly decrease TC/Pro ratio in foam cells in a concentration-dependent (0 mg/L: 36.9 +/- 1.1, 10.0 mg/L: 6.2 +/- 0.4, P < 0.01) and time-dependent (10.0 mg/L HDL(1) 6 h: 16.9 +/- 0.9, 24 h: 6.4 +/- 0.6, P < 0.01) manner.

CONCLUSIONHDL(1) is capable of inhibiting and attenuating the formation of foam cells by decreasing cellular TC, therefore, might play an important role in attenuating atherosclerosis.

Atherosclerosis ; Cells, Cultured ; Cholesterol, LDL ; metabolism ; Foam Cells ; cytology ; metabolism ; Humans ; Lipoproteins, HDL ; blood ; Lipoproteins, LDL ; Monocytes ; cytology ; metabolism

This study explores the regulatory effect of astragaloside Ⅳ on miR-17-5 p and its downstream proprotein convertase subtillisin/kexin type 9(PCSK9)/very low density lipoprotein receptor(VLDLR) signal pathway, aiming at elucidating the mechanism of astragaloside Ⅳ against atherosclerosis(AS). In cell experiment, oxidized low-density lipoprotein(ox-LDL) was used for endothelial cell injury modeling with vascular smooth muscle cells(VSMCs). Then cells were classified into the model group, miR-17-5 p inhibitor group, blank serum group, and astragaloside Ⅳ-containing serum group based on the invention. Afterward, cell viability and the expression of miR-17-5 p, VLDLR, and PCSK9 mRNA and protein in cells in each group were detected. In animal experiment, 15 C57 BL/6 mice were used as the control group, and 45 ApoE~(-/-) mice were classified into the model group, miR-17-5 p inhibitor group, and astragaloside Ⅳ group, with 15 mice in each group. After 8 weeks of intervention, the peripheral serum levels of interleukin-6(IL-6), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α), and the expression of miR-17-5 p, VLDLR, and PCSK9 mRNA in the aorta of mice were detected. The pathological changes of mice in each group were observed. According to the cell experiment, VSMC viability in the miR-17-5 p inhibitor group and the astragaloside Ⅳ-containing serum group was higher than that in the model group(P<0.05). The mRNA and protein expression of miR-17-5 p and VLDLR in VSMCs in the miR-17-5 p inhibitor group and the astragaloside Ⅳ-containing serum group was lower than that in the model group(P<0.05), but the mRNA and protein expression of PCSK9 was higher than that in the model group(P<0.05). As for the animal experiment, the levels of IL-6 and TNF-α in the peripheral serum of the miR-17-5 p inhibitor group and the astragaloside Ⅳ group were lower(P<0.05) and the serum level of IL-10 was higher(P<0.05) than that of the model group. The mRNA expression of miR-17-5 p and VLDLR in the aorta in the miR-17-5 p inhibitor group and the astragaloside Ⅳ group was lower(P<0.05), and PCSK9 mRNA expression was higher(P<0.05) than that in the model group. Pathological observation showed mild AS in the miR-17-5 p inhibitor group and the astragaloside Ⅳ group. In summary, astragaloside Ⅳ can prevent the occurrence and development of AS. The mechanism is that it performs targeted regulation of miR-17-5 p, further affecting the PCSK9/VLDLR signal pathway, inhibiting vascular inflammation, and thus alleviating endothelial cell injury.
Animals ; Atherosclerosis/genetics* ; Lipoproteins, LDL/metabolism* ; Mice ; MicroRNAs/metabolism* ; Proprotein Convertase 9/metabolism* ; Receptors, LDL/metabolism* ; Saponins ; Signal Transduction ; Triterpenes

OBJECTIVETo explore low density lipoprotein (LDL) oxidation by macrophage myeloperoxidase (MPO) at molecular level.

METHODSUsing a mouse macrophage model, we examined the relationship between LDL oxidation and macrophage MPO by measuring macrophage MPO activity, LDL oxidation products, MPO gene expression and cellular orientation of LDL oxidation.

RESULTSMPO gene expression increased to its maximum gradually when the concentration of LDL was increased, and then maintained at that level. NaN(3) inhibied the elevation of MPO activity and LDL oxidation, which was LDL concentration-dependent. After the composition of macrophage membrane was roughly analyzed, it was determined that the contents of MPO and LDL in 5% sucrose were 7.667 and 21 times higher than those in 10% sucrose, respectively.

CONCLUSIONLDL is attached to the "microdomain" of the macrophage membrane in which LDL is oxidized by MPO.

Animals ; Lipoproteins, LDL ; metabolism ; Macrophages ; metabolism ; Mice ; Oxidation-Reduction ; Peroxidase ; genetics ; metabolism

Animals ; Atherosclerosis ; etiology ; metabolism ; Gene Expression Regulation ; Humans ; Lipase ; analysis ; genetics ; physiology ; Lipoproteins ; metabolism ; Lipoproteins, HDL ; metabolism ; Lipoproteins, LDL ; metabolism ; Polymorphism, Genetic ; Tissue Distribution

Liver is one of the most important organs in energy metabolism. Most plasma apolipoproteins and endogenous lipids and lipoproteins are synthesized in the liver. It depends on the integrity of liver cellular function, which ensures homeostasis of lipid and lipoprotein metabolism. When liver cancer occurs, these processes are impaired and the plasma lipid and lipoprotein patterns may be changed. Liver cancer is the fifth common malignant tumor worldwide, and is closely related to the infections of hepatitis B virus (HBV) and hepatitis C virus (HCV). HBV and HCV infections are quite common in China and other Southeast Asian countries. In addition, liver cancer is often followed by a procession of chronic hepatitis or cirrhosis, so that hepatic function is damaged obviously on these bases, which may significantly influence lipid and lipoprotein metabolism in vivo. In this review we summarize the clinical significance of lipid and lipoprotein metabolism under liver cancer.
Animals ; Apolipoproteins ; metabolism ; Cholesterol ; metabolism ; Fatty Acids ; metabolism ; Humans ; Lipid Metabolism ; Lipoprotein(a) ; metabolism ; Lipoproteins, HDL ; metabolism ; Lipoproteins, LDL ; metabolism ; Liver Neoplasms ; metabolism ; Triglycerides ; metabolism

A preliminary study was performed to investigate the staining characteristics of trabecula. endothelial cells with low density lipoprotein (LDL) and acetylated low density lipoprotein (Ac-LDL) labeled with a fluorescent probe, 1, 1`- dioctadecyl-3,3,3`, 3`- tetramethyl-indocarbocyanine perchlorate (Dil). Trabecular endothelial cells revealed a strong fluorescence with Dil-LDL, which was contradictory to the previous results obtained from other types of endothelial cells. These cells also showed a moderate fluorescence with Dil-Ac-LDL. Scleral fibroblasts and keratocytes showed a moderate to strong fluorescence with Dil-LDL and a weak fluorescence with Dil-Ac-LDL. Corneal endothelial cells revealed a very weak background fluorescence with Dil-LDL and a moderate fluorescence with Dil-Ar-LDL. Therefore, these four kinds of cells could not be definitely differentiated depending only on the staining characteristics with Dil-LDL and Dil-Ac-LDt.
Animals ; Cattle ; Endothelium/cytology ; Fluorescent Dyes/*diagnostic use ; Lipoproteins, LDL/*metabolism ; Trabecular Meshwork/*metabolism

The role of very low density lipoprotein receptor (LVLDR) in the process of foam cell formation was investigated. After the primary cultured mouse peritoneal macrophages were incubated with VLDL, beta-VLDL or low density lipoprotein (LDL), respectively for 24 h and 48 h, foam cells formation was identified by oil red O staining and cellular contents of triglyceride (TG) and total cholesterol (TC) were determined. The mRNA levels of LDLR, LDLR related protein (ILRP) and VLDLR were detected by semi-quantitative RT-PCR. The results demonstrated that VLDL, beta-VLDL and LDL could increase the contents of TG and TC in macrophages. Cells treated with VLDL or beta-VLDL showed markedly increased expression of VLDLR and decreased expression of LDLR, whereas LRP was up-regulated slightly. For identifying the effect of VLDL receptor on cellular lipid accumulation, ldl-A7-VR cells, which expresses VLDLR and trace amount of LRP without functional LDLR, was used to incubate with lipoproteins for further examination. The results elucidated that the uptake of triglyceride-rich lipoprotein mediated by VLDLR plays an important role in accumulation of lipid and the formation of foam cells.
Animals ; Arteriosclerosis ; metabolism ; pathology ; Cells, Cultured ; Cholesterol, LDL ; metabolism ; pharmacology ; Female ; Foam Cells ; cytology ; metabolism ; Lipoproteins, VLDL ; pharmacology ; Macrophages, Peritoneal ; cytology ; metabolism ; Mice ; Receptors, LDL ; metabolism ; Triglycerides ; metabolism

BACKGROUND: A preponderance of small low-density lipoproteins (LDL subclass phenotype B) has been closely associated with a high-risk for coronary artery disease. Lipoprotein lipase (LPL) gene polymorphisms have been found to be associated with coronary artery disease and lipid levels; but their impact on LDL particle size is less clearly established. METHODS: The LDL subclass phenotype was analyzed in 114 normal controls and 131 patients with coronary artery disease using the LipoPrint LDL system (Quantimetrix Co., Redondo Beach, CA, USA). HindIII and PvuII polymorphisms of LPL genes were analyzed using PCR-RFLP. Ser447 -Ter polymorphisms of LPL gene were analyzed using the PCR-based method and using mismatched primer and restriction digestion. The analysis of their associations with the LDL subclass phenotype and the LDL score was investigated. RESULTS: No statistical differences in the allelic frequencies of HindIII, PvuII and Ser447 -Ter poly-morphisms were observed between the control and patient groups. The G allelic frequency of Ser447 -Ter polymorphism was significantly higher in phenotype B than in the phenotype AandI group (P=0.043). HindIII, PvuII and Ser447 -Ter sites were in strong linkage disequilibrium. CONCLUSIONS: HindIII, PvuII and Ser447 -Ter polymorphisms were not directly linked with coronary artery disease. However, the Ser447 -Ter polymorphism is associated with the small LDL particle, which results in a change in lipid metabolism and might have an effect on the development of coronary artery disease.
Coronary Artery Disease* ; Coronary Vessels* ; Digestion ; Humans ; Linkage Disequilibrium ; Lipid Metabolism ; Lipoprotein Lipase* ; Lipoproteins* ; Lipoproteins, LDL ; Particle Size ; Phenotype

To observe the effect of oxidized low density lipoprotein (OxLDL) on arterial endothelial cells apoptosis in vivo, we established a model in which Sprague-Dawley rats were given intraperitoneal and intravenous injection of unmodified LDL (8 mg/kg every day) via the tail vein. Seven days after the injection, the aortic endothelial cells specimens were prepared by an en face preparation of rat aorta. The apoptotic cells were identified and counted by in situ nick and labelling (TUNEL) method and light microscopy. The numbers of the apoptotic cells were 12.52 +/- 4.71/field in the intraperitoneal injection control group, 11.41 +/- 2.94/field in the intravenous injection control group, 22.98 +/- 8.01/field in the intraperitoneal injection LDL group and 103.8 +/- 11.5/field in the intravenous injection LDL group, respectively. The difference was significant between injection LDL group and control (P < 0.01), and the difference was also significant between two LDL injection groups (P < 0.01). These findings suggest that injection of LDL can induce apoptosis in arterial endothelial cells and the effect is especially significant with intravenous injection LDL. After injection, oxidative modification of LDL may occur in local arteries and causes injury to the endothelial cells.
Aorta ; Apoptosis/*drug effects ; Endothelium, Vascular/*pathology ; In Situ Nick-End Labeling ; Injections, Intraperitoneal ; Injections, Intravenous ; Lipoproteins, LDL/*metabolism ; Lipoproteins, LDL/*pharmacology ; Oxidation-Reduction ; Random Allocation ; Rats, Sprague-Dawley