scholarly journals Dietary-Induced Elevations of Triglyceride-Rich Lipoproteins Promote Atherosclerosis in the Low-Density Lipoprotein Receptor Knockout Syrian Golden Hamster

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiao Lin ◽  
Ping Ma ◽  
Chun Yang ◽  
Jinjie Wang ◽  
Kunxiang He ◽  
...  
Keyword(s):  
Golden Hamster ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Syrian Golden Hamster ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Low Density Lipoprotein Receptor ◽  
Large Particles ◽  
Density Lipoprotein Receptor

Elevated triglycerides are associated with an increased risk of cardiovascular disease (CVD). Therefore, it is very important to understand the metabolism of triglyceride-rich lipoproteins (TRLs) and their atherogenic role in animal models. Using low-density lipoprotein receptor knockout (LDLR−/−) Syrian golden hamsters, this study showed that unlike LDLR−/− mice, when LDLR−/− hamsters were fed a high cholesterol high-fat diet (HFD), they had very high plasma levels of triglycerides and cholesterol. We found that LDLR−/− hamsters exhibited increased serum TRLs and the ApoB100 and 48 in these particles after being fed with HFD. Treatment with ezetimibe for 2 weeks decreased these large particles but not the LDL. In addition, ezetimibe simultaneously reduced ApoB48 and ApoE in plasma and TRLs. The expression of LRP1 did not change in the liver. These findings suggested that the significantly reduced large particles were mainly chylomicron remnants, and further, the remnants were mainly cleared by the LDL receptor in hamsters. After 40 days on an HFD, LDLR−/− hamsters had accelerated aortic atherosclerosis, accompanied by severe fatty liver, and ezetimibe treatment reduced the consequences of hyperlipidemia. Compared with the serum from LDLR−/− hamsters, that from ezetimibe-treated LDLR−/− hamsters decreased the expression of vascular adhesion factors in vascular endothelial cells and lipid uptake by macrophages. Our results suggested that in the LDLR−/− hamster model, intestinally-derived lipoprotein remnants are highly atherogenic and the inflammatory response of the endothelium and foam cells from macrophages triggered atherosclerosis. The LDL receptor might be very important for chylomicrons remnant clearance in the Syrian golden hamster, and this may not be compensated by another pathway. We suggest that the LDLR−/− hamster is a good model for the study of TRLs-related diseases as it mimics more complex hyperlipidemia.

scholarly journals Low-Density Lipoprotein Receptor-Related Proteins in Skeletal Development and Disease

2017 ◽  
Vol 97 (3) ◽  
pp. 1211-1228 ◽  
Author(s):  
Tao Yang ◽  
Bart O. Williams
Keyword(s):  
Skeletal Development ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Protein Family ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Low Density Lipoprotein Receptor ◽  
Density Lipoprotein Receptor

The identification of the low-density lipoprotein receptor (LDLR) provided a foundation for subsequent studies in lipoprotein metabolism, receptor-mediated endocytosis, and many other fundamental biological functions. The importance of the LDLR led to numerous studies that identified homologous molecules and ultimately resulted in the description of the LDL-receptor superfamily, a group of proteins that contain domains also found in the LDLR. Subsequent studies have revealed that members of the LDLR-related protein family play roles in regulating many aspects of signal transduction. This review is focused on the roles of selected members of this protein family in skeletal development and disease. We present background on the identification of this subgroup of receptors, discuss the phenotypes associated with alterations in their function in human patients and mouse models, and describe the current efforts to therapeutically target these proteins to treat human skeletal disease.

scholarly journals Synthesis and properties of the very-low-density-lipoprotein receptor and a comparison with the low-density-lipoprotein receptor

1997 ◽  
Vol 324 (2) ◽  
pp. 371-377 ◽  
Author(s):  
Dilip D. PATEL ◽  
Robert A. FORDER ◽  
Anne K. SOUTAR ◽  
Brian L. KNIGHT
Keyword(s):  
Cho Cells ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Low Density Lipoprotein Receptor ◽  
Vldl Receptor ◽  
Density Lipoprotein Receptor

The properties of the very-low-density lipoprotein (VLDL) receptor have been studied in Chinese hamster ovary (CHO) cells stably transfected with human VLDL-receptor cDNA and compared with those of the low-density lipoprotein (LDL) receptor expressed under the same conditions. Immunoblotting showed that the cells produced a mature VLDL receptor protein, of apparent Mr 123000 on non-reduced and 158000 on reduced gels, that was less extensively glycosylated than the LDL receptor. The VLDL receptor was more slowly processed than the LDL receptor, with only approx. 70% of the precursor being converted into the mature protein. Nevertheless, the majority of the receptor in the cells was in the mature form, and most of this was present on the cell surface. The human VLDL receptor bound rabbit very-low-density lipoprotein with β electrophoretic mobility (βVLDL), but not human LDL, and uptake through the receptor led to stimulation of oleate incorporation into cholesteryl esters. At 37 °C, the characteristics of VLDL-receptor-mediated uptake and degradation of βVLDL were essentially the same as those mediated by the LDL receptor. However, the VLDL receptor apparently did not show the increase in affinity and decrease in binding of βVLDL on cooling to 4 °C that was exhibited by the LDL receptor. Thus the overexpressed VLDL receptor in CHO cells appears to behave as a lipoprotein receptor with similar, but not identical, properties to the LDL receptor.

scholarly journals Uptake and esterification of exogenous cholesterol by low-density-lipoprotein-receptor-negative human fibroblasts in culture

1984 ◽  
Vol 222 (3) ◽  
pp. 821-824 ◽  
Author(s):  
J P Slotte ◽  
S Ekman ◽  
S Björkerud
Keyword(s):  
Exchange Rate ◽  
Low Density Lipoprotein ◽  
Human Fibroblasts ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Low Density Lipoprotein Receptor ◽  
Exogenous Cholesterol ◽  
Density Lipoprotein Receptor

The incorporation and metabolism of both vesicle- and LDL (low-density lipoprotein)- derived [3H]cholesterol by LDL-receptor-negative fibroblasts were studied. Independent of the cholesterol source, free [3H]cholesterol was readily incorporated into the cells and was available for esterification. 7-Oxocholesterol stimulated both [3H]cholesterol incorporation, by increasing the exchange rate, and the subsequent esterification of it irrespective of the source of exogenous [3H]cholesterol. The 7-oxocholesterol-stimulated esterification of exogenously derived LDL free [3H]cholesterol was progesterone-sensitive and energy-requiring.

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