The Very Low-density Lipoprotein (VLDL) Receptor: Characterization and Functions as a Peripheral Lipoprotein Receptor

Takahashi, Sadao; Sakai, Juro; Fujino, Takahiro; Hashimoto, Hiroaki; Zenimaru, Yasuo; Suzuki, Jinya; Miyamori, Isamu; Yamamoto, Tokuo

doi:10.5551/jat.11.200

Cited by 157 publications

(122 citation statements)

References 53 publications

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“…Both of VLDLR and LRP5/6 belong to the LDL receptor gene family (50,51), but the interactions between VLDLR and LRP5/6 have not been reported previously. Several ligands for VLDLR have been identified previously, including plasminogen inhibitor type 1, thrombospondin-1, and tissue factor pathway inhibitor (52).…”

Section: Discussionmentioning

confidence: 99%

Very Low Density Lipoprotein Receptor, a Negative Regulator of the wnt Signaling Pathway and Choroidal Neovascularization

Chen

et al. 2007

Journal of Biological Chemistry

112

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Choroidal neovascularization (CNV) in age-related macular degeneration is a leading cause of blindness. Very low density lipoprotein receptor gene knock-out (Vldlr ؊/؊ ) mice have been shown to develop subretinal neovascularization (NV) with an unknown mechanism. The present study showed that in Vldlr ؊/؊ mice, NV initiated in the choroid and progressed to penetrate the retinal pigment epithelium layer, proliferating in the subretinal space. This phenotype recapitulated what is seen in wet age-related macular degeneration, suggesting that this is a CNV model. The CNV correlated with overexpression of vascular endothelial growth factor in Vldlr ؊/؊ eyecups and was blocked by a neutralizing antibody against vascular endothelial growth factor receptor-2. The wnt co-receptor LRP5/6 expression was significantly up-regulated in Vldlr ؊/؊ eyecups compared with that in wild-type mice. Significantly, Vldlr ؊/؊ mice showed impaired phosphorylation of downstream effectors of the wnt signaling pathway, glycogen synthase kinase-3␤ (GSK-3␤), and ␤-catenin, concomitant with increased levels of free GSK-3␤ and ␤-catenin, suggesting an increased activity of the wnt pathway. Down-regulation of VLDLR by small interference RNA resulted in up-regulation of LRP5/6 expression and activation of ␤-catenin in cultured endothelial cells. Furthermore, Dickkopf-1, a specific inhibitor of the wnt pathway, effectively decreased vascular endothelial growth factor and ␤-catenin levels in the retinal pigment epithelium of Vldlr ؊/؊ mice and in cells transfected with the VLDLR small interference RNA. These results suggest that VLDLR functions as a negative regulator of CNV, and this function is mediated through the wnt pathway.

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Section: Discussionmentioning

confidence: 99%

Very Low Density Lipoprotein Receptor, a Negative Regulator of the wnt Signaling Pathway and Choroidal Neovascularization

Chen

et al. 2007

Journal of Biological Chemistry

112

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“…In the population at large, the e2 and the e4 alleles have been linked to high triglyceride levels [19][20][21]31]. The LDL receptor recognises ApoE and ApoB-100 and plays a crucial role in cholesterol homeostasis [32], whereas the structurally related very LDL receptor recognises ApoE, but not ApoB-100, and plays an important role in triglyceride metabolism [33]. In the present study, serum triglycerides were affected by both the severity of sleep disordered breathing and APOE genotype and, importantly, these differences remained significant after adjustments for BMI and other covariates.…”

Section: Discussionmentioning

confidence: 99%

Effects of apolipoprotein E genotype on serum lipids in obstructive sleep apnoea

et al. 2013

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There is increasing evidence that intermittent hypoxia resulting from obstructive sleep apnoea (OSA) is independently associated with dyslipidaemia. Currently, no data exist on potential links between OSA-related dyslipidaemia and susceptibility genes for dyslipidaemia in such patients. Our aim was to study the effects of the apolipoprotein E (APOE) genotype and sleep apnoea severity on atherogenic dyslipidaemia in patients with OSA.519 clinically stable subjects prospectively recruited at a tertiary referral teaching hospital underwent full polysomnography. APOE gene polymorphisms were assessed using real-time PCR.In all APOE genotype groups, serum triglycerides increased while high-density lipoprotein (HDL) cholesterol was reduced with increasing severity of OSA in each APOE genotype group, whereas the deleterious effects of OSA on serum apolipoprotein (Apo)B levels were observed in e2 carriers and the e3/e3 genotype only. Nevertheless, the e4 allele carriers had ApoB levels within the risk range, irrespective of nocturnal hypoxia. In addition, among patients with the high-risk e4 genotype, those with the most severe nocturnal hypoxia had significantly higher triglyceride and lower HDL cholesterol levels compared with nonhypoxic e4 subjects. APOE genotype and the oxygen desaturation index were both independent predictors of serum triglyceride levels (p50.009 and p,0.001, respectively; R 2 50.148) and ApoB levels (p50.001 and p50.003, respectively; R 2 50.104). Our findings suggest that OSA has adverse effects on several lipid parameters over and above the effects carried by APOE genotype. Further st1udies are needed to analyse the effects of high-risk genotypes on metabolic and cardiovascular outcomes in patients with OSA. @ERSpublications OSA has adverse effects on several lipid parameters in addition to the effects carried by the APOE genotype

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“…On the other hand, MS subjects showed a high incidence of abnormal plaque quality, such as plaque eccentricity, calcification and lipid pools. Therefore, even though each component of MS plays an important role in the progression of atherosclerosis [21][22][23][24] , the Japanese criteria of MS, which stress visceral fat accumulation, is a reasonable definition to detect the population at high risk for acute coronary syndrome, and we should detect and treat MS subjects as early as possible. Some reports have emphasized that insulin resistance is a central factor in the pathogenesis of MS 25,26) , and insulin resistance is also known to play an important role in the progression of coronary atherosclerosis [27][28][29][30] .…”

Section: Significance Of Ms For Plaque Formation In Early Stage Coronmentioning

confidence: 99%

Relationship between Metabolic Syndrome and Early Stage Coronary Atherosclerosis

Hatori

Takahashi

Iizuka

et al. 2007

JAT

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Aim: Recent clinical studies using intra-vascular ultrasound have clarified that coronary artery plaque already exists in subjects with normal coronary artery which is diagnosed by coronary angiography; furthermore, culprit lesion on acute coronary syndrome often occurs in mild to moderate angiographical stenotic lesion. The aim of this study is to clarify relationship between metabolic syndrome and early stage coronary atherosclerosis using a 3-dimensional intra-vascular ultrasound. Methods: 70 subjects with normal coronary artery diagnosed by coronary angiography were enrolled. Proxymal range of left anterior descending coronary artery was observed by intra-vascular ultrasound using autopullback methods. Results: Subjects with metabolic syndrome had significantly high percent plaque volume (31 8% vs 21 8%, p 0.0001) and frequently detected abnormal plaque quality such as eccentricity, calcification and lipid pool into plaque than those without metabolic syndrome. Multivariate analysis showed that serum adiponectin concentration was the most strongest variable for percent plaque volume (t value 3.0, p 0.01). On the other hand, subjects with hypoadiponectinemia were detected high incidence of mild calcification into plaque.

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The Very Low-density Lipoprotein (VLDL) Receptor: Characterization and Functions as a Peripheral Lipoprotein Receptor

Abstract: The very low-density lipoprotein (VLDL) receptor is a member of the low-density lipoprotein (LDL) receptor family. In vitro and in vivo studies

Cited by 157 publications

References 53 publications

Very Low Density Lipoprotein Receptor, a Negative Regulator of the wnt Signaling Pathway and Choroidal Neovascularization

Very Low Density Lipoprotein Receptor, a Negative Regulator of the wnt Signaling Pathway and Choroidal Neovascularization

Effects of apolipoprotein E genotype on serum lipids in obstructive sleep apnoea

Relationship between Metabolic Syndrome and Early Stage Coronary Atherosclerosis

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