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Lipoproteins, LDLReceptors, LDLCholesterol, LDLApolipoproteins BCholesterolLipoproteinsApolipoprotein B-100Hyperlipoproteinemia Type IITriglyceridesOxidation-ReductionLipoproteins, VLDLCholesterol EstersArteriosclerosisHypercholesterolemiaLipidsLipoproteins, HDLCholesterol, HDLApolipoproteinsParticle SizeReceptors, LipoproteinApolipoproteins ECholesterol, VLDLLipid PeroxidationHyperlipidemiasVitamin ELipoproteins, IDLAnticholesteremic AgentsFoam CellsReceptors, ScavengerCholesterol, DietaryLipid PeroxidesMacrophagesThiobarbituric Acid Reactive SubstancesCells, CulturedAtherosclerosisLipoprotein(a)Hyperlipidemia, Familial CombinedAortaAntioxidantsApolipoprotein A-ILovastatinScavenger Receptors, Class BEsterificationHypertriglyceridemiaProbucolLiverDietary FatsHydroxymethylglutaryl-CoA Reductase InhibitorsLow Density Lipoprotein Receptor-Related Protein-1UltracentrifugationProprotein ConvertasesKineticsAntigens, CD36Diet, AtherogenicCholesterol Ester Transfer ProteinsRabbitsLysophosphatidylcholinesEndothelium, VascularHeptanoic AcidsHypolipidemic AgentsMalondialdehydeAryldialkylphosphataseMonocytes1-Alkyl-2-acetylglycerophosphocholine EsteraseColestipolFibroblastsScavenger Receptors, Class ALipid MetabolismSimvastatinApolipoprotein C-IIIElectrophoresis, Agar GelLipoprotein LipaseSterol O-AcyltransferaseIodine RadioisotopesApolipoproteins APravastatinHyperlipoproteinemiasReference ValuesSterolsChylomicronsPhospholipidsPlant OilsBlood Component RemovalPhosphatidylcholine-Sterol O-AcyltransferasePhytosterolsDyslipidemiasThiobarbituratesMacrophages, PeritonealHydroxycholesterolsReceptors, ImmunologicKetocholesterolsHypochlorous AcidFatty AcidsRNA, MessengerCoronary DiseasePyrrolesDiet, Fat-RestrictedEndocytosisCross-Over StudiesArachidonate 15-Lipoxygenase
LDLRProteinTriglyceridesHigh-density lipMiceDefectiveGeneDegradationLiverPCSK9EndocytosisHepaticMutationsMetabolismApoBVLDLLipoproteinsLigandsParticlesFamilial hypercholesterolaemiaDisorderCell-surfaceApolipoprotein B-1HypercholesterolemiaLevelsProteinsAffinitySmall denseOLR1BoundStatinsBindsDecreaseBile acidsApoEParticleDisruptionLipidTotal
LDLR14
  • In humans, the LDL receptor protein is encoded by the LDLR gene on chromosome 19. (wikipedia.org)
  • Individuals with disruptive mutations (defined as nonsense, splice site, or indel frameshift) in LDLR have an average LDL-cholesterol of 279 mg/dL, compared with 135 mg/dL for individuals with neither disruptive nor deleterious mutations. (wikipedia.org)
  • This protein belongs to the LDLR family and is made up of a number of functionally distinct domains, including 3 EGF-like domains, 7 LDL-R class A domains, and 6 LDL-R class B repeats. (wikipedia.org)
  • We previously identified the E3 ubiquitin ligase IDOL as a sterol-dependent regulator of the LDL receptor (LDLR). (kent.ac.uk)
  • The low-density lipoprotein receptor (LDLR) is an important factor in maintaining cholesterol homeostasis by the receptor-mediated endocytosis of LDL particles. (currentmedicinalchemistry.com)
  • Defective hepatic LDLR activity and uptake of LDL particles lead to elevated blood levels of low-density lipoprotein cholesterol (LDL-C), which is associated with a higher risk of atherosclerotic cardiovascular disease. (currentmedicinalchemistry.com)
  • PCSK9 (proprotein convertase subtilisin/kexin 9) increases low-density lipoprotein (LDL)-cholesterol levels via LDL receptor (LDLR) degradation. (elsevierpure.com)
  • Ng lipoproteins are taken up by two functionally significant low-density lipoprotein (LDL) receptors: the prototypic LDL receptor (LDLR) along with the LDL receptor-related protein 1 (LRP1). (nicotinic-receptor.com)
  • BACKGROUND: Rare mutations of the low-density lipoprotein receptor gene (LDLR) cause familial hypercholesterolemia, which increases the risk for coronary artery disease (CAD). (uni-luebeck.de)
  • METHODS: Imputed genotype data at the LDLR locus on 1 644 individuals of a population-based sample were explored for association with LDL-C level. (uni-luebeck.de)
  • Replication of association with LDL-C level was sought for the most significant single nucleotide polymorphism (SNP) within the LDLR gene in three European samples comprising 6 642 adults and 533 children. (uni-luebeck.de)
  • Adjustment for LDL-C levels by logistic regression or Mendelian Randomisation models abolished the significant association between rs2228671 with CAD completely, indicating a functional link between the genetic variant at the LDLR gene locus, change in LDL-C and risk of CAD. (uni-luebeck.de)
  • CONCLUSION: A common variant at the LDLR gene locus affects LDL-C levels and, thereby, the risk for CAD. (uni-luebeck.de)
  • Apolipoprotein E (apoE) is an important determinant for tile uptake of triglyceride-rich emulsions and lipuproteins hy the liver, and exerts affinity for both the LDL receptor (LDLr) and a distinct liver-specific recognition site. (zhangqiaokeyan.com)
Protein14
  • The low-density lipoprotein receptor (LDL-R) is a mosaic protein of 839 amino acids (after removal of 21-amino acid signal peptide) that mediates the endocytosis of cholesterol-rich low-density lipoprotein (LDL). (wikipedia.org)
  • e.g. a truncation of the receptor protein at residue number 660 leads to domains 3,4 and 5 of the EGF precursor domain being missing. (wikipedia.org)
  • This precludes the movement of the receptor from the ER to the Golgi, and leads to degradation of the receptor protein. (wikipedia.org)
  • This gene encodes a member of the low-density lipoprotein receptor related protein family. (nih.gov)
  • Effect of hyperglycemia and hyperlipidemia on atherosclerosis in LDL receptor-deficient mice: establishment of a combined model and association with heat shock protein 65 immunity. (diabetesjournals.org)
  • Affimer' synthetic protein scaffolds block oxidized LDL binding to the LOX-1 scavenger receptor and inhibit ERK1/2 activation. (bvsalud.org)
  • Genetic disruption of multidrug resistance-associated protein 1 improves endothelial function and attenuates atherosclerosis in MRP1-/- LDL-/- double knockout mice. (escardio.org)
  • An ELISA was used to quantify LDL-receptor protein in total cell membranes. (psu.edu)
  • Here, we report that in AD patients and two mouse models of AD, overexpression of serum response factor (SRF) and myocardin (MYOCD) in cerebral vascular smooth muscle cells (VSMCs) generates an Aβ non-clearing VSMC phenotype through transactivation of sterol regulatory element binding protein-2, which downregulates low density lipoprotein receptor-related protein-1, a key Aβ clearance receptor. (nature.com)
  • ED1 , encoding a ligand-ectodysplasinA-A1 (EDA-A1), EDAR , coding for ectodysplasinA-A1 receptor, EDARADD , programming the structure of EDAR-associated death domain protein and NEMO whose protein product, NFκB essential modulator (NEMO), is necessary for an indirect activation of nuclear factor κB (NFκB). (springer.com)
  • Signaling is initiated when the Wnt ligand binds to the Frizzled receptor on the cell membrane and the LDL receptor-associated protein 5/6 (LRP5/6) co-receptor. (frontiersin.org)
  • Low density lipoprotein (LDL) is normally bound at the cell membrane and taken into the cell ending up in lysosomes where the protein is degraded and the cholesterol is made available for repression of microsomal enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting step in cholesterol synthesis. (thermofisher.com)
  • Apolipoprotein B is the main protein component of LDL and accounts for approximately 95% of the total protein content of LDL. (cdc.gov)
  • Lipoprotein (a) (Lp[a]) consists of an LDL-like particle with apoprotein B and a side chain of a highly glycosylated protein. (medscape.com)
Triglycerides9
High-density lip2
  • Nicotinic acid raises high-density lipoprotein (HDL) cholesterol levels while lowering total cholesterol, LDL cholesterol, and triglyceride levels. (cdc.gov)
  • In this study, we investigated the associations between proteins related to CVD and triglyceride (TG), total cholesterol, LDL (low-density lipoprotein), and HDL (high-density lipoprotein) cholesterol levels in individuals from the general population. (lu.se)
Mice5
  • In the current study, we established a model combining hyperglycemia with hyperlipidemia in LDL receptor-deficient (LDL-RD) mice and assessed its possible influences on lipid profile, HSP60/65, and atherogenesis. (diabetesjournals.org)
  • LDL-RD mice were injected either with streptozotocin to induce hyperglycemia or with citrate buffer (control). (diabetesjournals.org)
  • In conclusion, we have established a mouse model that combines hyperglycemia with diet-induced hyperlipidemia in LDL-RD mice and studied its effect on atherosclerosis progression. (diabetesjournals.org)
  • Methods and results Atherosclerosis-associated parameters were analyzed in LDL receptor deficient mice fed HFD for 12 weeks alone or supplemented with Lab4P. (cardiff.ac.uk)
  • Glutaredoxin 2a overexpression in macrophages promotes mitochondrial dysfunction but has little or no effect on atherogenesis in LDL-receptor null mice. (ox.ac.uk)
Defective1
  • Familial LDL receptor deficiency and familial defective apoprotein B-100 are examples of primary defects that can lead to the accumulation of LDL, which corresponds to a type IIa pattern of hyperlipidemia. (medscape.com)
Gene8
  • It belongs to the low density lipoprotein receptor gene family. (wikipedia.org)
  • Mutations in the gene encoding the LDL receptor are known to cause familial hypercholesterolaemia. (wikipedia.org)
  • Here we report that antidiabetic thiazolidinediones (TZDs) and other ligands for the nuclear receptor PPARγ dramatically upregulate oxidized LDL receptor 1 (OLR1) in adipocytes by facilitating the exchange of coactivators for corepressors on the OLR1 gene in cultured mouse adipocytes. (jci.org)
  • It's rare, but when both parents pass on the gene to their child, LDL levels are dangerously high. (upmc.com)
  • The low density lipoprotein receptor (LDL-R) gene family consists of cell surface proteins involved in receptor-mediated endocytosis of specific ligands. (thermofisher.com)
  • Mutations in the LDL-R gene cause the autosomal dominant disorder, familial hypercholesterolemia. (thermofisher.com)
  • Separate guidelines should be created for severe and homozygous FH, defined as either the presence of LDL cholesterol levels 400 mg/dL or greater or a pathogenic gene variant in any of the FH-related genes on two different alleles. (cdc.gov)
  • IGF-I deficiency can be the result of GH resistance or insensitivity due to genetic disorders of the GH receptor causing GH receptor deficiency (growth hormone receptor deficiency [GHRD], Laron syndrome) or postreceptor defects, including the principal transduction agent STAT5b, the IGF-I/IGFBP3 stabilizer acid labile subunit (ALS), the IGF-I gene, or the IGF-I receptor. (medscape.com)
Degradation2
  • The IDOL-UBE2D complex mediates sterol-dependent degradation of the LDL receptor. (kent.ac.uk)
  • Phagocytosis is a term coined from the Greek to describe the receptor-mediated engulfment and degradation of dead cells and microbes. (frontiersin.org)
Liver5
  • They may also increase removal of LDL particles and increase apoA-I and apoA-II in the liver which may contribute to increase in HDL cholesterol levels. (cdc.gov)
  • In the liver, cholesterol and plant sterols may be transported to peripheral tissues by very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL), converted to bile acids, or transported out of the liver into the bile for excretion. (medscape.com)
  • The nuclear hormone receptors liver X receptor α (LXRα) and LXRβ function as physiological receptors for oxidized cholesterol metabolites (oxysterols) and regulate several aspects of cholesterol and lipid metabolism. (aspetjournals.org)
  • Apo B is necessary for the reaction with LDL receptors in the liver and on cell walls, and is thus involved in transporting cholesterol from the liver to the vessel cell. (cdc.gov)
  • LDL is removed from the circulation primarily by the liver through the LDL receptor. (medscape.com)
PCSK94
  • A combination of unbiased global transcriptomics and new network-based hyperedge entanglement prediction analysis identified the NF-κB (nuclear factor-kappa B) signaling molecules, lectin-like oxidized LOX-1 (LDL receptor-1), and SDC4 (syndecan-4) as potential PCSK9 targets mediating pro-inflammatory responses in macrophages. (elsevierpure.com)
  • Medicines called PCSK9 inhibitors lower cholesterol-increasing LDL receptors. (cdc.gov)
  • By studying outliers in this population, Dr. Hobbs identified a genetic defect in PCSK9 that is responsible for low plasma LDL levels. (jci.org)
  • She also discusses the initiation of the Dallas Heart Study and the development of a therapeutic inhibitor of PCSK9 for lowering LDL. (jci.org)
Endocytosis2
  • The cytosolic C-terminal domain contains ~50 amino acids, including a signal sequence important for localizing the receptors to clathrin-coated pits and for triggering receptor-mediated endocytosis after binding. (wikipedia.org)
  • Following receptor-mediated endocytosis, ApoE is recycled for the plasma membrane, and cholesterol is used for cell membrane turnover and repair, myelin formation, synaptogenesis and neurotransmitter release [146]. (nicotinic-receptor.com)
Hepatic1
  • To examine this directly in humans, we studied the effects of lowering dietary saturated fat on LDL-receptor abundance in peripheral mononuclear cells which reflects hepatic LDL-receptor status. (psu.edu)
Mutations5
  • There are 5 broad classes of mutation of the LDL receptor: Class 1 mutations affect the synthesis of the receptor in the endoplasmic reticulum (ER). (wikipedia.org)
  • Class 2 mutations prevent proper transport to the Golgi body needed for modifications to the receptor. (wikipedia.org)
  • The majority and most severe FH cases are associated to mutations in the receptor for low-density lipoproteins receptor (LDL-r), but the molecular basis explaining the connection between mutation and phenotype is often unknown, which hinders early diagnosis and treatment of the disease. (upf.edu)
  • We have used atomistic simulations to explore the complete SNP mutational space (227 mutants) of the LA5 repeat, the key domain for interacting with LDL that is coded in the exon concentrating the highest number of mutations. (upf.edu)
  • Combining our simulations with available structural data from different laboratories, we have defined a consensus-binding site for the interaction of the LA5 repeat with LDL-r partner proteins and have found that most (16) of the 17 stable FH mutations occur at binding site residues. (upf.edu)
Metabolism3
  • Michael S. Brown and Joseph L. Goldstein were awarded the 1985 Nobel Prize in Physiology or Medicine for their identification of LDL-R and its relation to cholesterol metabolism and familial hypercholesterolemia. (wikipedia.org)
  • These findings indicate the critical role of miRNAs in regulating LDL metabolism. (currentmedicinalchemistry.com)
  • Reduction of total cholesterols (TC) and LDL-C by dietary alterations and medications that affect lipid metabolism [ 14 ] is found to reduce the occurrence of atherosclerosis in animals and clinical cardiovascular events in human [ 15 ]. (hindawi.com)
ApoB2
  • 0.001) with serum levels of LDL-cholesterol (r = -0.747) and apoB (r = =0.593). (psu.edu)
  • The second is an apolipoprotein(a) which is bound to the LDL-like molecule at the ApoB receptor with a disulfide bond. (medscape.com)
VLDL4
  • It is a cell-surface receptor that recognizes apolipoprotein B100 (ApoB100), which is embedded in the outer phospholipid layer of very low-density lipoprotein (VLDL), their remnants-i.e. intermediate-density lipoprotein (IDL), and LDL particles. (wikipedia.org)
  • Lab4P increased plasma HDL and triglyceride levels and decreased LDL/VLDL levels. (cardiff.ac.uk)
  • Lipoproteins may be classified according to their density, as follows: chylomicrons, very-low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). (medscape.com)
  • HDL particles that contain apoproteins A-I and A-II interact with other lipoproteins, particularly VLDL and LDL, through lipolysis and the action of lecithin cholesterol acyltransferase (LCAT) enzyme. (medscape.com)
Lipoproteins1
Ligands1
  • These proteins also serve as ligands to specific receptors, they facilitate transmembrane transport, and they regulate enzymatic activity. (medscape.com)
Particles1
  • The chemical modification by oxidation of these particles can trigger pathological responses, mediated by a group of membrane proteins termed scavenger receptors . (bvsalud.org)
Familial hypercholesterolaemia1
  • Molecular basis of familial hypercholesterolaemia from structure of LDL receptor module. (expasy.org)
Disorder1
  • For someone with the disorder, LDL levels are high from birth or childhood. (upmc.com)
Cell-surface1
  • The GH molecule binds to its specific cell surface receptor (GHR), which dimerizes with another GHR molecule so that the single GH molecule is enveloped by 2 GHR molecules. (medscape.com)
Apolipoprotein B-11
Hypercholesterolemia1
Levels11
  • Plasma fasting glucose, lipid profile, and antibody levels to HSP65 and oxidized LDL were assessed. (diabetesjournals.org)
  • Studies with animal models suggest that saturated fatty acids raise low density lipoprotein (LDL)-cholesterol levels by reducing LDL receptor- mediated clearance. (psu.edu)
  • A dose-dependent reduction in LDL-C levels with oat cereals supports the independent hypocholesterolemic effects of beta-glucan. (greenmedinfo.com)
  • Phytosterols have been shown to reduce serum and plasma total cholesterol and LDL levels in healthy individuals. (medscape.com)
  • A healthy diet and active lifestyle can help manage the disease, but they aren't enough to lower LDL levels on their own. (upmc.com)
  • You may also need other medicine, such as ezetimibe, to lower LDL levels even more. (upmc.com)
  • they were treated with the drug for 24 weeks, resulting in reductions of low density lipoprotein (LDL) cholesterol of almost 54%, with nearly 42% reaching target levels. (medscape.com)
  • By studying outliers in the Dallas Heart Study, Hobbs ( Figure 1 ) uncovered a genetic defect responsible for low blood LDL cholesterol levels. (jci.org)
  • Screening may be based on cholesterol levels or positive genetic tests for an LDL receptor function defect. (cdc.gov)
  • Proof of benefit is strongest for lowering elevated low-density lipoprotein cholesterol (LDL-C) levels. (msdmanuals.com)
  • This system does not take into account specific lipoprotein abnormalities (eg, low HDL-C or high LDL-C) that may contribute to disease despite normal cholesterol and TG levels. (msdmanuals.com)
Proteins1
  • The intact receptor lacks tyrosine kinase activity, but binding of GH and dimerization results in association with JAK2, a member of the Janus kinase family, which results in self-phosphorylation of the JAK2 and a cascade of phosphorylation of cellular proteins. (medscape.com)
Affinity1
  • Although the insulin receptor has a low affinity for IGF-I, IGF-I is present in the circulation at molar concentrations that are 1000 times those of insulin. (medscape.com)
Small dense1
OLR12
  • TZDs markedly stimulate the uptake of oxidized LDL (oxLDL) into adipocytes, and this requires OLR1. (jci.org)
  • Here, we describe an association of the 3′-UTR +1073 C/T polymorphism of the OLR1 (oxidised LDL receptor 1) on chromosome 12 with AD in French sporadic (589 cases and 663 controls) and American familial (230 affected sibs and 143 unaffected sibs) populations. (bmj.com)
Bound2
  • It is thought that this region is responsible for the pH-dependent conformational shift that causes bound LDL to be released in the endosome. (wikipedia.org)
  • Molecular modeling indicated that the LOX-1-specific Affimers bound predominantly via their variable loop regions to the surface of the LOX-1 lectin -like domain that contains a distinctive arrangement of arginine residues previously implicated in oxLDL binding, involving interactions with both subunits of the native, stable scavenger receptor homodimer. (bvsalud.org)
Statins1
  • If you look at LDL cholesterol trials where they gave statins to control LDL, the best predictor at that point of recurrent events was actually the lipoprotein(a) level, not the LDL level. (medscape.com)
Binds1
  • The lectin -like oxidized low-density lipoprotein (LOX-1) scavenger receptor binds to oxidized low-density lipoprotein (oxLDL) and mediates both signaling and trafficking outcomes. (bvsalud.org)
Decrease4
  • This results in a decrease in LDL cholesterol circulating in the bloodstream. (cdc.gov)
  • In summary, reducing dietary saturated fat is associated with an increase in LDL-receptor abundance of magnitude similar to the decrease in serum LDL-cholesterol. (psu.edu)
  • Thus, an important mechanism by which reductions in dietary saturated fatty acids decrease LDL-cholesterol in humans is through an increase in LDL- receptor number. (psu.edu)
  • Pharmacologic therapy for osteoporosis includes most commonly the use of antiresorptive agents to decrease bone resorption, such as bisphosphonates, denosumab, and the selective estrogen-receptor modulator (SERM) raloxifene. (medscape.com)
Bile acids1
ApoE2
  • The receptor also recognizes apolipoprotein E (ApoE) which is found in chylomicron remnants and IDL. (wikipedia.org)
  • Both the ratio of apoE:C on the emulsions upon serum incubation and the alpha-helical content of apoE were inversely correlated with particle size, indicating that these factors may be involved in tile emulsion size-dependent receptor specificity in vivo. (zhangqiaokeyan.com)
Particle1
Disruption1
  • Disruption of LDL-R can lead to higher LDL-cholesterol as well as increasing the risk of related diseases. (wikipedia.org)
Lipid1
  • Among these associations, we found KIM-1 (kidney injury molecule-1), TNFR (TNF [tumor necrosis factor] receptor) 1 and 2, TRAIL-R2 (TRAIL [TNF-related apoptosis-inducing ligand] receptor 2), and RETN (resistin) to be associated with all 4 lipid fractions. (lu.se)
Total2