K Domain CR9 of Low Density Lipoprotein (LDL) Receptor-related Protein 1 (LRP1) Is Critical for Aggregated LDL-induced Foam Cell Formation from Human Vascular Smooth Muscle Cells

Costales, Paula; Fuentes‐Prior, Pablo; Castellano, José; Revuelta‐López, Elena; Corral-Rodríguez, María Ángeles; Nasarre, Laura; Badimon, Lina; Llorente‐Cortés, Vicenta

doi:10.1074/jbc.m115.638361

Cited by 48 publications

(34 citation statements)

References 69 publications

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“…However, although all strains showed similar 125 I-Aβ 40 clearance, analysis of proteins expression showed SJL/J mice to have lower level of LRP1, which suggests species differences in the expression, trafficking, or degradation of this protein at the BBB. Interestingly, available studies showed a positive direct correlation between LRP1 expression and vascular lipid disposition in atherosclerosis, this correlation is consistent with our findings of low LRP1 level in SJL/J mice which are known to be resistant for the development of atherosclerotic lesions [20, 21]. …”

Section: Discussionsupporting

confidence: 93%

Effect of mouse strain as a background for Alzheimer’s disease models on the clearance of amyloid-β

Qosa

Kaddoumi

2016

J Integr Syst Neurosci

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Novel animal models of Alzheimer’s disease (AD) are relentlessly being developed and existing ones are being fine-tuned; however, these models face multiple challenges associated with the complexity of the disease where most of these models do not reproduce the full phenotypical disease spectrum. Moreover, different AD models express different phenotypes that could affect their validity to recapitulate disease pathogenesis and/or response to a drug. One of the most important and understudied differences between AD models is differences in the phenotypic characteristics of the background species. Here, we used the brain clearance index (BCI) method to investigate the effect of strain differences on the clearance of amyloid β (Aβ) from the brains of four mouse strains. These mouse strains, namely C57BL/6, FVB/N, BALB/c and SJL/J, are widely used as a background for the development of AD mouse models. Findings showed that while Aβ clearance across the blood-brain barrier (BBB) was comparable between the 4 strains, levels of LRP1, an Aβ clearance protein, was significantly lower in SJL/J mice compared to other mouse strains. Furthermore, these mouse strains showed a significantly different response to rifampicin treatment with regard to Aβ clearance and effect on brain level of its clearance-related proteins. Our results provide for the first time an evidence for strain differences that could affect ability of AD mouse models to recapitulate response to a drug, and opens a new research avenue that requires further investigation to successfully develop mouse models that could simulate clinically important phenotypic characteristics of AD.

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Section: Discussionsupporting

confidence: 93%

Effect of mouse strain as a background for Alzheimer’s disease models on the clearance of amyloid-β

Qosa

Kaddoumi

2016

J Integr Syst Neurosci

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“…To generate DiI-oxLDL, a stock solution of the fluorescent probe: 1,1′-dioctadecyl-3,3,3′,3-tetramethylindocarbocyanine perchlorate (DiI, Molecular Probes Invitrogen, Carlsbad, CA) was prepared in DMSO and then added to the LDL solution to yield a final ratio of 1 μg of DiI/mg of oxLDL. The mixture was incubated for 18 h at 37 °C under light protection, as previously described [ 61 ]. Cells were incubated with HG or NG in M199 medium containing 0.2% SBF ( v / v ) for 72 h and with DiI-oxLDL (5 µg/mL) for the last 24 h. To test the specificity of uptake, the VSMC were treated with DiI-oxLDL and an excess of unlabeled oxLDL.…”

Section: Methodsmentioning

confidence: 99%

Role of the Scavenger Receptor CD36 in Accelerated Diabetic Atherosclerosis

Navas‐Madroñal

Castelblanco

Camacho

et al. 2020

IJMS

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Diabetes mellitus entails increased atherosclerotic burden and medial arterial calcification, but the precise mechanisms are not fully elucidated. We aimed to investigate the implication of CD36 in inflammation and calcification processes orchestrated by vascular smooth muscle cells (VSMCs) under hyperglycemic and atherogenic conditions. We examined the expression of CD36, pro-inflammatory cytokines, endoplasmic reticulum (ER) stress markers, and mineralization-regulating enzymes by RT-PCR in human VSMCs, cultured in a medium containing normal (5 mM) or high glucose (22 mM) for 72 h with or without oxidized low-density lipoprotein (oxLDL) (24 h). The uptake of 1,1′-dioctadecyl-3,3,3′,3-tetramethylindocarbocyanine perchlorate-fluorescently (DiI) labeled oxLDL was quantified by flow cytometry and fluorimetry and calcification assays were performed in VSMC cultured in osteogenic medium and stained by alizarin red. We observed induction in the expression of CD36, cytokines, calcification markers, and ER stress markers under high glucose that was exacerbated by oxLDL. These results were confirmed in carotid plaques from subjects with diabetes versus non-diabetic subjects. Accordingly, the uptake of DiI-labeled oxLDL was increased after exposure to high glucose. The silencing of CD36 reduced the induction of CD36 and the expression of calcification enzymes and mineralization of VSMC. Our results indicate that CD36 signaling is partially involved in hyperglycemia and oxLDL-induced vascular calcification in diabetes.

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“…In general, modified LDLs can be bound and internalized by different cell surface receptors, such as scavenger receptors (LOX-1, scavenger receptor A (SRA), and CD36) and LRP1. The LRP1 receptor is the main one responsible for binding and internalizing aggLDL, whereas scavenger receptors can recognize other forms of modified LDLs [ 15 , 39 , 52 ]. However, LRP1 participation in the processing of other modified lipoproteins can not be discarded, since macrophages are able to incorporate diverse modified LDLs (mainly oxLDL), with LRP1 being necessary for these cells to become foam cells [ 53 ].…”

Section: Lrp1 In the Metabolic Syndromementioning

confidence: 99%

“…Based on its ability to exert complex and multi-molecular extra- and intracellular functions, LRP1 has been shown to be involved in MetS. In this way, this receptor plays a key role in the uptake and processing of modified and non-modified lipoproteins in different tissues, which is associated with the promotion of intracellular lipid accumulation occurring during dyslipidemia [ 15 , 16 , 17 ]. In glucose homeostasis, LRP1 has a regulatory action on the insulin receptor (IR) and GLUT4 activation [ 10 , 16 , 18 ], which has been strongly associated with insulin resistance developed during MetS.…”

Section: Introductionmentioning

confidence: 99%

The Role of Low-Density Lipoprotein Receptor-Related Protein 1 in Lipid Metabolism, Glucose Homeostasis and Inflammation

Dato

Chiabrando

2018

IJMS

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Metabolic syndrome (MetS) is a highly prevalent disorder which can be used to identify individuals with a higher risk for cardiovascular disease and type 2 diabetes. This metabolic syndrome is characterized by a combination of physiological, metabolic, and molecular alterations such as insulin resistance, dyslipidemia, and central obesity. The low-density lipoprotein receptor-related protein 1 (LRP1—A member of the LDL receptor family) is an endocytic and signaling receptor that is expressed in several tissues. It is involved in the clearance of chylomicron remnants from circulation, and has been demonstrated to play a key role in the lipid metabolism at the hepatic level. Recent studies have shown that LRP1 is involved in insulin receptor (IR) trafficking and intracellular signaling activity, which have an impact on the regulation of glucose homeostasis in adipocytes, muscle cells, and brain. In addition, LRP1 has the potential to inhibit or sustain inflammation in macrophages, depending on its cellular expression, as well as the presence of particular types of ligands in the extracellular microenvironment. In this review, we summarize existing perspectives and the latest innovations concerning the role of tissue-specific LRP1 in lipoprotein and glucose metabolism, and examine its ability to mediate inflammatory processes related to MetS and atherosclerosis.

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K Domain CR9 of Low Density Lipoprotein (LDL) Receptor-related Protein 1 (LRP1) Is Critical for Aggregated LDL-induced Foam Cell Formation from Human Vascular Smooth Muscle Cells

Cited by 48 publications

References 69 publications

Effect of mouse strain as a background for Alzheimer’s disease models on the clearance of amyloid-β

Effect of mouse strain as a background for Alzheimer’s disease models on the clearance of amyloid-β

Role of the Scavenger Receptor CD36 in Accelerated Diabetic Atherosclerosis

The Role of Low-Density Lipoprotein Receptor-Related Protein 1 in Lipid Metabolism, Glucose Homeostasis and Inflammation

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