The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index; 1 of the 28 sources its claims cite were checked for support.
Upregulation of the low density lipoprotein receptor at the blood-brain barrier: intercommunications between brain capillary endothelial cells and astrocytes.
Open accessAbstract
In contrast to the endothelial cells in large vessels where LDL receptors are downregulated, brain capillary endothelial cells in vivo express an LDL receptor. Using a cell culture model of the blood-brain barrier consisting of a coculture of brain capillary endothelial cells and astrocytes, we observed that the capacity of endothelial cells to bind LDL is enhanced threefold when cocultured with astrocytes. We next investigated the ability of astrocytes to modulate endothelial cell LDL receptor expression. We have shown that the lipid requirement of astrocytes increases the expression of endothelial cell LDL receptors. Experiments with dialysis membranes of different pore size showed that this effect is mediated by a soluble factor(s) with relative molecular mass somewhere between 3,500 and 14,000. Substituting astrocytes with smooth muscle cells or brain endothelium with endothelium from the aorta or the adrenal cortex did not enhance the luminal LDL receptor expression on endothelial cells, demonstrating the specificity of the interactions. This factor(s) is exclusively secreted by astrocytes cocultured with brain capillary endothelial cells, but it also upregulates the LDL receptor on other cell types. This study confirms the notion that the final fine tuning of cell differentiation is under local control.
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Written from the paper’s full text.
TL;DR
Brain capillary endothelial cells express LDL receptors at confluence despite high lipoprotein levels, unlike aortic endothelial cells, and coculture with astrocytes increases their LDL binding capacity. Astrocytes depleted of cholesterol release a soluble factor(s) of 3,500–14,000 mol wt that upregulates endothelial LDL receptor expression via new receptor synthesis.
Key findings
- LDL binding to brain capillary endothelial cells was enhanced threefold when cocultured with astrocytes; maximal binding was 358 ng LDL/mg protein with astrocytes versus 215 ng LDL/mg protein without, with apparent Kd values of 43 nM versus 90 nM, respectively.
- Cholesterol depletion of astrocytes by 36 h in lipoprotein-deficient serum decreased astrocyte cholesterol content by 32% (27.00 ± 3.37 vs 39.25 ± 4.03 µg cholesterol/mg protein, n = 6) and led to upregulation of endothelial LDL receptors, reaching a maximum of 600% of control binding at 4–5 h.
- Astrocyte-conditioned medium increased LDL binding by 300% at 4–5 h; upregulation occurred with a 14,000 mol wt cutoff dialysis membrane but not with a 3,500 cutoff, indicating a soluble factor(s) between 3,500 and 14,000 mol wt.
- The effect was specific: substituting astrocytes with smooth muscle cells or brain endothelium with aortic or adrenal cortex endothelium did not enhance luminal LDL receptor expression; acetylated LDL/scavenger receptor binding was not upregulated, and cycloheximide blocked the increase, indicating new LDL receptor synthesis.
Methods
- Bovine brain capillary endothelial cells were cocultured with rat astrocytes on opposite sides of collagen-coated filter inserts; astrocytes were >95% GFAP positive. Bovine aortic endothelial cells, adrenal cortex endothelial cells, and smooth muscle cells were used for specificity comparisons.
- LDL binding was performed at 4°C with [125I]LDL, with nonspecific binding determined by 20-fold excess unlabeled LDL; Scatchard analysis, C7 monoclonal antibody blocking, acetylated LDL binding, and HPLC cholesterol measurement were used.
- Regulation experiments followed four phases: 12 d coculture in 15% calf serum, 36 h astrocyte incubation in 10% lipoprotein-deficient serum, induction with cholesterol-depleted astrocytes or conditioned medium at 37°C, then LDL binding at 4°C; dialysis membranes with 3,500 or 14,000 mol wt cutoffs and cycloheximide (10 µg/ml) were used in modified induction experiments.
Limitations
- The paper states that the chemical nature of the astrocyte-regulating LDL receptor factor(s) is under investigation, that additional studies are underway to determine whether bound lipoproteins are degraded or transcytosed, and that 36 h LPDS incubation was used because cell lysis could be detected after 48 h.
- The paper also notes that upregulation was lower with astrocyte-conditioned medium, possibly because the secreted molecule(s) is unstable.
- Evident from the text: the findings rely on an in vitro bovine/rat coculture model, the soluble factor is not purified or chemically identified, and in vivo confirmation is not provided.
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
1 of 28 cited sources checked · 0 supported · 0 flagged · accuracy not yet measured
- Findingnone given§ Discussion
Aortic endothelial cells and adrenal cortex endothelial cells cultured in the same medium do not express this LDL receptor at confluence.
“Since aortic ECs and adrenal cortex ECs cultured in the same medium do not express this LDL receptor at confluence”
Quote in the paperSubstantial claim - Findingown data§ Results
Pretreatment of astrocytes with LPDS leads to a time-dependent increase in the binding of [125I]LDL to the cells.
“The pretreat- ment of astrocytes with LPDS led to a time-dependent in- crease in the binding of [t2SI]LDL to the cells (Fig. 4), indi- cating that the cells have modified their metabolism to obtain more exogenous cholesterol.”
Quote in the paperSubstantial claim - Findingreasoning§ Discussion
AUF has no effect if endothelial cells are incubated with cycloheximide.
“Furthermore, the AUF has no effect if ECs are incubated with cycloheximide.”
Quote in the paperSubstantial claim - Findingown data§ Discussion
When aortic endothelial cells or adrenal cortex endothelial cells were cocultivated with astrocytes, no effect on upregulation of LDL receptors was observed when astrocytes were fed with LPDS.
“when aortic ECs, originating from peripheral large vessels, or adrenal cortex ECs, origi- nating from peripheral microvessels, were cocultivated with astrocytes, no effect on the upregulation of the LDL recep- tors was observed when astrocytes were fed with LPDS.”
Quote in the paperSubstantial claim - Findingown data§ Discussion
Labeled LDL bound specifically to brain capillary endothelial cells that were 5 d postconfluence and in the presence of a medium containing 15% calf serum.
“labeled LDL bound specifically to brain capillary ECs that were 5 d postconfluence (as visualized by phase contrast mi- croscopy) and in the presence of a medium containing 15 % calf serum.”
Quote in the paperSubstantial claim
- Findingown data§ Results
Smooth muscle cells did not induce an upregulation of LDL receptors on brain capillary endothelial cells.
“Similarly, SMC did not induce an upregulation of LDL receptors on brain capillary ECs (data not shown).”
Quote in the paperSubstantial claim - Findingown data§ Discussion
When astrocytes were pre-incubated in lipoprotein-deficient medium before the induction phase, binding of LDL to endothelial cells increased a further sixfold.
“When astrocytes were pre-incubated in lipoprotein-deficient medium before the induction phase, binding of LDL to en- dothelial cells was increased a further sixfold.”
Quote in the paperSubstantial claim - Findingown data§ Abstract
The factor(s) also upregulates the LDL receptor on other cell types.
“This factor(s) is exclusively secreted by astrocytes cocultured with brain capillary endothelial cells, but it also upregulates the LDL receptor on other cell types.”
Quote in the paperNot a substantial claim - Findingown data§ Discussion
The capacity of endothelial cells to bind LDL is greater when cocultured with astrocytes than in their absence.
“Our findings also showed that the capacity of ECs to bind LDL is greater when cocultured with astrocytes than in their absence.”
Quote in the paperSubstantial claim - Findingown data§ Results
When binding of acetylated LDL is performed instead of LDL to brain capillary endothelial cells, no upregulation of the scavenger receptor occurs.
“Furthermore, when binding of acetylated LDL is per- formed instead of LDL to brain capillary ECs, no upregula- tion of the scavenger receptor occurs (Fig. 9).”
Quote in the paperNot a substantial claim - Findingown data§ Abstract
Coculturing brain capillary endothelial cells with astrocytes enhances their capacity to bind LDL approximately threefold.
“Using a cell culture model of the blood-brain barrier consisting of a coculture of brain capillary endothelial cells and astrocytes, we observed that the capacity of endothelial cells to bind LDL is enhanced threefold when cocultured with astrocytes.”
Quote in the paperSubstantial claim - Findingown data§ Results
Maximal LDL binding was higher when brain capillary endothelial cells were cocultured with astrocytes (358 ng LDL/mg protein) than when cultured alone (215 ng LDL/mg protein).
“However, the maximal binding was higher (358 ng LDL/mg protein) when the ECs were cocultured with astrocytes than when they were cultured alone (215 ng LDL/mg protein).”
Quote in the paperSubstantial claim - Findingown data§ Results
When brain capillary endothelial cells were incubated with cycloheximide during the induction phase, no increase in LDL receptor expression was observed.
“When brain capillary ECs were incubated with cycloheximide during the”
Quote in the paperSubstantial claim - Findingown data§ Results
Labeled LDL bound with saturation kinetics on brain capillary endothelial cells cultured alone or cocultured with astrocytes in 15% calf serum, in contrast to aortic endothelial cells.
“Labeled LDL bound with saturation kinetic on brain capri- lary ECs cultured alone or cocultured with astrocytes in 15 % CS, in contrast to what was observed on aortic endothelial cells (Fig. 3).”
Quote in the paperSubstantial claim - Findingown data§ Discussion
AUF(s) secreted by astrocytes triggered the appearance of specific binding on aortic endothelial cells and smooth muscle cells, even when they were cultured at confluence and in the presence of a high concentration of lipoproteins.
“The results showed that the AUF(s) secreted by astrocytes triggered the appearance of specific binding on aortic ECs and smooth muscle cells, even when they were cultured at confluence and in the presence of a high concen- tration of lipoproteins.”
Quote in the paperSubstantial claim - Findingown data§ Abstract
The lipid requirement of astrocytes increases the expression of endothelial cell LDL receptors.
“We have shown that the lipid requirement of astrocytes increases the expression of endothelial cell LDL receptors.”
Quote in the paperSubstantial claim - Findingown data§ Results
HPLC analysis shows a 32% decrease in the cholesterol content of astrocytes (27.00 ± 3.37 μg cholesterol/mg protein vs 39.25 ± 4.03 μg/mg protein, n=6) when incubated at 37°C for 36 h in LPDS.
“Furthermore, HPLC analysis shows a 32 % decrease of the cholesterol content of astro- cytes (27.00 + 3.37 #g cholesterol/rag protein vs 39.25 + 4.03 #g cholesterol/mg protein, n = 6), when they were in- cubated at 37C for 36 h in LPDS.”
Quote in the paperSubstantial claim - Findingown data§ Discussion
Scatchard analysis revealed, for cultures with or without astrocytes, a single class of high-affinity LDL binding sites on brain capillary endothelial cells with a Kd of the order of nM.
“These data revealed, for the culture with or without astrocytes, the presence on brain cap- illary ECs of a single class of high affinity LDL binding sites with a Kd of the order of riM.”
Quote in the paperSubstantial claim - Findingown data§ Results
No specific binding was observed on aortic endothelial cells cultured alone.
“No specific binding was ob- served on aortic ECs cultured alone”
Quote in the paperSubstantial claim - Findingown data§ Results
Specific binding of LDL to aortic endothelial cells increases greatly when they are in the presence of cholesterol-depleted astrocytes.
“we could see a large increase in the specific binding of the LDL to the aortic ECs when they were in the presence of cholesterol-depleted astro- cytes”
Quote in the paperSubstantial claim - Findingown data§ Results
There is an increase in the number of LDL receptors on brain capillary endothelial cells in the presence of astrocytes.
“Furthermore, there was an increase in the num- ber of the LDL receptors on brain capillary ECs in the pres- ence of astrocytes.”
Quote in the paperSubstantial claim - Findingown data§ Results
No upregulation of LDL receptors on aortic endothelial cells and adrenal cortex endothelial cells was observed when astrocytes were cultured in LPDS for 36 h.
“Under these conditions, no upregulation on aortic ECs and adrenal cortex ECs was observed when the astrocytes were cultured in LPDS for 36 h (data not shown).”
Quote in the paperSubstantial claim - Findingown data§ Discussion
Substituting astrocytes with smooth muscle cells in coculture did not enhance the expression of LDL receptors on brain capillary endothelial cells.
“we have also shown this kind of specific interaction because substituting astrocytes with smooth muscle cells in coculture did not enhance the expression of the LDL receptors on brain capillary ECs.”
Quote in the paperSubstantial claim - Findingown data§ Discussion
Astrocytes cultured alone do not upregulate LDL receptors on brain capillary endothelial cells during the induction phase.
“Furthermore, astrocytes cultured alone do not up- regulate LDL receptors on brain capillary ECs during the induction phase.”
Quote in the paperSubstantial claim - Premisecitation§ Introduction
In vivo, normal circulating concentrations of lipoproteins downregulate LDL receptor levels on vascular endothelial cells.
“In vivo, normal circulating concentration of lipoproteins downregulates the LDL receptor levels on vas- cular endothelial cells (ECs).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Vasile et al., 1983 source
- Interpretationown data§ Abstract
The astrocyte effect on endothelial LDL receptor expression is mediated by a soluble factor(s) with relative molecular mass between 3,500 and 14,000.
“Experiments with dialysis membranes of different pore size showed that this effect is mediated by a soluble factor(s) with relative molecular mass somewhere between 3,500 and 14,000.”
Quote in the paperSubstantial claim - Interpretationnone given§ Discussion
The molecule(s) responsible for upregulation could not be a product of cell lysis during incubation with LPDS.
“As already stated for the upregulation of the LDL receptor, the mole- cule(s) could not be a product of the cell lysis that could oc- cur during the incubation with LPDS.”
Quote in the paperNot a substantial claim - Interpretationown data§ Introduction
A soluble factor(s) derived from astrocytes modulates LDL receptor expression at the luminal surface of the brain capillary endothelium.
“We docu- ment specific EC-astrocyte interactions, and we propose that a soluble factor(s) derived from astrocytes modulates LDL receptor expression at the luminal surface of the brain capillary endothelium.”
Quote in the paperSubstantial claim - Interpretationown data§ Results
Reciprocal communications between endothelial cells and astrocytes are required to activate the mechanism of upregulation during the coculture phase.
“Reciprocal communications between ECs and as- trocytes are required to activate the mechanism of the up- regulation during the coculture phase.”
Quote in the paperSubstantial claim - Interpretationreasoning§ Discussion
The LDL receptor was present at the luminal side of endothelial cells.
“This LDL recep- tor was present at the luminal side of ECs.”
Quote in the paperSubstantial claim - Interpretationown data§ Discussion
Brain endothelium and astrocytes interact specifically in vitro to induce expression of the LDL receptor at the luminal side of brain capillary endothelial cells.
“the two close neighbors in vivo, brain endotheliumand astrocytes, interact specifically in vitro to induce the expres- sion of the LDL receptor at the luminal side of brain capil- lary ECs.”
Quote in the paperSubstantial claim - Interpretationown data§ Discussion
A soluble factor(s) is involved in the upregulation mechanism.
“The significant conclusion from the cholesterol-depleted astro- cyte conditioned medium experiments is that a soluble fac- tor(s) is involved in the upregulation mechanism.”
Quote in the paperSubstantial claim - Premisecitation§ Discussion
The affinity estimate is similar to that reported by Vlodasky et al. in bovine aortic endothelial cells cultured in lipoprotein-deficient serum (Kd = 27 nM).
“This estimate of affinity is similar to that reported by Vlodasky et al. (1978) in bovine aortic ECs cultured in lipoprotein deficient serum (Kd = 27 nM).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Vlodasky et al. (1978)
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Study design and conductcitation§ Introduction
The in vitro model of the blood-brain barrier imitates an in vivo situation by culturing brain capillary endothelial cells and astrocytes on opposite sides of a filter.
“In attempts to investigate such interactions, we have developed an in vitro model of the blood-brain barrier that imitates an in vivo situation by culturing brain capillary ECs and astrocytes on opposite sides of a filter (Dehouck et al., 1990a, 1992).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Dehouck et al., 1990a, 1992
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationcitation§ Discussion
The discrepancy may be related to the origin of the endothelial cells (brain capillaries).
“This discrepancy may be related to the origin of the ECs (brain capillaries)”
Quote in the paperSubstantial claim - Premisecitation§ Introduction
Cultured brain capillary endothelial cells have LDL receptors with the same apparent molecular weight as in vivo.
“In addition, we have shown that cultured brain capillary ECs have LDL receptors with the same apparent molecular weight as in vivo (Meresse et al., 1991).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Meresse et al., 1991 source
- Premisecitation§ Discussion
Endothelial cells in culture express an LDL receptor with the same apparent molecular weight as that in vivo (132,000 D).
“We have determined (M6resse et al., 1991) by ligand blotting that ECs in culture express an LDL receptor with the same apparent molecular weight as that in vivo (132,000 D).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites M6resse et al., 1991
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Premisecitation§ Discussion
The receptor exhibits the same characteristic properties as the LDL receptor on human fibroblasts.
“This receptor exhibits the same characteristic properties as the LDL receptor on human fibroblasts (Goldstein and Brown, 1977).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Goldstein and Brown, 1977 source
- Interpretationreasoning§ Abstract
The study confirms the notion that the final fine tuning of cell differentiation is under local control.
“This study confirms the notion that the final fine tuning of cell differentiation is under local control.”
Quote in the paperSubstantial claim - Premisecitation§ Introduction
Astrocytes induce some of the specialized properties of endothelial cells.
“Astroeytes, the nearest neighbor of brain capillaries, have been shown to in- duce some of the specialized properties of ECs (Janzer and Raft, 1987).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Janzer and Raft, 1987
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationown data§ Discussion
The cerebral endothelial receptor plays a role in cholesterol transport across the blood-brain barrier.
“Our results integrated into this model, and they strongly sug- gest that the cerebral endothelial receptor plays a role in cho- lesterol transport across the blood-brain barrier.”
Quote in the paperSubstantial claim - Interpretationown data§ Discussion
The lipid requirement of astrocytes modulates the expression of endothelial cell LDL receptors.
“This result indicates that the lipid requirement of astrocytes modulates the expression of endothelial cell LDL receptors.”
Quote in the paperSubstantial claim - Interpretationreasoning§ Discussion
The culture medium used could not have been responsible for the absence of downregulation observed with brain capillary endothelial cells.
“the culture medium used could not have been responsible for the absence of downregulationobserved with brain capillary ECs.”
Quote in the paperSubstantial claim - Premisecitation§ Introduction
The LDL receptor on brain capillary endothelial cells exhibits the same characteristic properties as the LDL receptor on human fibroblasts.
“This receptor exhibits the same characteristic properties as the LDL recep- tor on human fibroblasts (Goldstein and Brown, 1977).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Goldstein and Brown, 1977 source
- Interpretationown data§ Abstract
The factor(s) is exclusively secreted by astrocytes cocultured with brain capillary endothelial cells.
“This factor(s) is exclusively secreted by astrocytes cocultured with brain capillary endothelial cells, but it also upregulates the LDL receptor on other cell types.”
Quote in the paperSubstantial claim - Premisecitation§ Discussion
Capillary endothelial cells differ from endothelial cells of other vessels in their biochemical and functional characteristics.
“several authors have shown that capillary ECs differ from the ECs of other vessels in their biochemical and functional characteristics (Zetter, 1988).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Zetter, 1988
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationreasoning§ Discussion
AUF seems to regulate LDL receptor expression specifically.
“So, the AUF seems to regulate LDL receptor expres- sion specifically.”
Quote in the paperSubstantial claim - Interpretationown data§ Discussion
The upregulation is caused by new synthesis of the LDL receptor.
“These results show that the upregula- tion is caused by new synthesis of the LDL receptor.”
Quote in the paperSubstantial claim- Rests on an assumption: Aortic endothelial cells and smooth muscle cells have no intracellular pool of LDL receptor.
- Rests on an assumption: Cycloheximide inhibits peptidyl transferase on the eukaryotic large ribosomal subunit and therefore protein synthesis in the cell.
- Interpretationreasoning§ Discussion
A cross-talk takes place between brain capillary endothelial cells and astrocytes during the coculture.
“This indicated that a cross-talk takes place between brain capillary ECs and astrocytes during the cocul- ture.”
Quote in the paperSubstantial claim - Study design and conductnone given§ Discussion
In the experimental conditions, only the abluminal face was in contact with LPDS.
“In our experimental conditions, only the albuminal face was in contact with LPDS”
Quote in the paperSubstantial claim - Premisecitation§ Discussion
Tight junctions, well developed in the coculture, prevent [125I]LDL leak into the abluminal compartment when the experiment is performed at 4C.
“tight junctions, very well developed in our coculture (Dehouck et al., 1990a), prevent [~ff]LDL leak into the abluminal com- partment when the experiment is performed at 4C (data not shown).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Dehouck et al., 1990a
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
- Interpretationreasoning§ Discussion
The study confirms the notion that endothelial cells generally do not express their final destination-specific differentiated features until these features are induced by local, environment-produced conditions.
“This study confirms the notion that endothelial ceils gener- ally not express their final destination-specific differentiated features until these features are induced by local, environ- ment-produced conditions.”
Quote in the paperNot a substantial claim - Interpretationown data§ Results
Binding of LDL on brain capillary endothelial cells is mediated by the LDL receptor.
“suggesting that binding on endothelial ceils is mediated by the receptor.”
Quote in the paperSubstantial claim - Interpretationcitation§ Discussion
Observations that brain endothelial cells can increase the incidence of intramembraneous particle arrays in astrocytes are in agreement with the results showing that endothelial cells can induce changes in associated glia.
“The observations that brain ECs can increase the inci- dence of intramembraneous particle arrays in astrocytes (Tao-Cheng et al., 1990) are in agreement with our results showing that endothelial cells can in turn induce changes in associated glia.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Tao-Cheng et al., 1990 source
- Interpretationown data§ Discussion
Because the EC-astrocyte effects are cross-species (bovine-rat), they are likely to be a fundamental property of the two cell types.
“Since these EC-astrocyte effects are a cross- species (bovine-rat), it is likely to be a fundamental property of the two cell types.”
Quote in the paperNot a substantial claim - Interpretationown data§ Results
The 12 d of coculture are necessary for enhanced LDL binding.
“Considered together, these results indicate that the 12 d of the coculture are necessary for enhanced LDL binding.”
Quote in the paperSubstantial claim - Interpretationown data§ Discussion
The binding results indicate that the receptor being studied is an LDL receptor.
“These results indicate that we are dealing with an LDL receptor.”
Quote in the paperSubstantial claim - Premisecitation§ Discussion
These modifications result from specific interactions between brain capillary endothelial cells and brain parenchyma.
“These modificationsresult from specific inter- actions between brain capillary ECs and brain parenchyma (Risau et al., 1986; Stewart and Wiley, 1981).”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationown data§ Discussion
The experiments using conditioned medium demonstrate that coculture increases the probability of detecting the effects of a short-lived agent produced by astrocytes.
“The experiments using conditioned medium clearly dem- onstrate that coculmre increases the probability of detecting the effects of a short-lived agent produced by astrocytes.”
Quote in the paperSubstantial claim
- Probably not a substantial claim. 14
- It may state two separate claims as one. 15
Probably not a substantial claim. It may state two separate claims as one.
Premisecitation§ IntroductionBrain capillary endothelial cells constitute the blood-brain barrier, are sealed together by high electrical resistance tight junctions, and display a low rate of transcellular vesicular transport.
“Brain capillary ECs, which constitute the blood-brain barrier, are sealed together by high electrical resistance tight junctions, and they display a low rate of transcellular vesicular trans- pert (Reese and Karnovsky, 1967).”
Quote in the paperSubstantial claim1 of 1 sources checked- cites Reese and Karnovsky, 1967 source
The Discussion (pp. 211–213) identifies cerebral endothelium as the barrier, describes apparently continuous tight junctions, and reports few transport-associated vesicles and no observed peroxidase discharge beyond the endothelium. It assesses junction tightness structurally, not by electrical-resistance measurement; that specific qualifier is unsupported. (LLM, conf=0.88)
Experimental — accuracy not yet measured
It may state two separate claims as one.
Findingown data§ DiscussionBrain capillary endothelial cells bind specifically acetylated LDL, but astrocytes cocultured with brain capillary endothelial cells for 12 d and fed LPDS cannot upregulate scavenger receptor expression on the brain capillary endothelial cell surface.
“although brain capillary ECs bind specif- ically acetylated LDL, astrocytes cocultured with brain cap- illary ECs for 12 d and fed with LPDS cannot upregulate scavenger receptor expression on brain capillary ECs sur- face.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown data§ DiscussionChanging a complete serum-containing medium to a medium containing 10% LPDS 36 h before binding depleted astrocyte cholesterol and upregulated apolipoprotein (B, E) receptor expression.
“when a complete serum-containing medium was changed to a medium containing 10% LPDS 36 h before the binding ex- periments, the cholesterol content of the astrocytes was depleted, and the expression of the apolipoprotein (B, E) receptors was upregulated.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown data§ ResultsNo increase in LDL receptor expression was observed in coculture with a cut-off membrane of 3,500, whereas upregulation was observed with a cut-off membrane of 14,000.
“No increase of LDL receptor expression was observed in the coculture with a cut-off membrane of 3,500. In contrast, the upregulation was observed in the coculture with a cut-off membrane of 14,000 (Fig. 7).”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown data§ ResultsThe C7 monoclonal antibody totally blocked the binding of LDL to bovine brain capillary endothelial cells, whereas control irrelevant IgG had no effect.
“The C7-monoclonai antibody, known to interact with the rl~ceptor binding domain, totally blocked the binding of LDL to bovine brain capillary ECs. Control irrelevant IgG had no effecton LDL binding (results not shown)”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Findingown data§ ResultsBrain capillary endothelial cells form a monolayer of small, tightly packed, nonoverlapping, contact-inhibited cells.
“ECs form a monolayer of small, tightly packed, nonoverlap- ping and contact-inhibited cells.”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown data§ DiscussionUpregulation experiments performed with smooth muscle cells instead of astrocytes, or with astrocytes not cocultured with brain capillary endothelial cells, did not enhance LDL receptor expression even if astrocytes were fed LPDS during the induction phase.
“upregulation experi- ments performed with SMC plated instead of astrocytes, or with astrocytes not cocultured with brain capillary ECs, did not enhance LDL receptor expression, even if astrocytes were fed with LPDS during the induction phase.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown data§ ResultsBrain capillary endothelial cells at confluence, cultured in a medium containing lipoproteins, express LDL receptors, in contrast to aortic endothelial cells.
“These results indicate that brain capillary ECs at con- fluence, cultured in a medium containing lipoproteins, ex- press LDL receptors in contrast to what was observed on aortic ECs.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown data§ ResultsIncreased binding of lipoproteins was already manifested 3 h after coculture of brain capillary endothelial cells and cholesterol-depleted astrocytes at 37°C, and the maximum effect (600% of control binding) was observed at 4 and 5 h.
“As shown in Fig. 5, increased binding of lipoproteins was al- ready manifested 3 h after coculture of the two cell types at 37C, and the maximum effect(600% of the control binding) was observed at 4 and 5 h.”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Premisecitation§ DiscussionAstrocytes possess an apo (B, E) receptor that provides a regulated mechanism for supplying cells with cholesterol.
“Like other cells in the body, astrocytes possess an apo (B, E) receptor, and at the cellular level, this receptor provides a regulated mechanism for supplying cells with cholesterol (Volpe et al., 1978; Pitas et al., 1987).”
Quote in the paperNot a substantial claim0 of 2 sources checkedIt may state two separate claims as one.
Interpretationreasoning§ DiscussionSecretion of the factor requires cocultured cells, indicating that reciprocal differentiation of both cell types might happen.
“The secretion of this factor re- quires cocultured cells, indicating that the reciprocal differ- entiation of both cell types might happen.”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Interpretationnone given§ DiscussionThe lower upregulation observed with astrocyte conditioned medium could be explained by secretion of an unstable molecule(s) by astrocytes.
“The fact that the up- regulation is lower when the astrocyte conditioned medium was used could be explained by the secretion of an unstable molecule(s) by astrocytes.”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Premisecitation§ IntroductionGrowing endothelial cells in culture bind LDL.
“A number of different studies have confirmed that growing ECs in culture also bind LDL (Vlodavsky et al., 1978).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Vlodavsky et al., 1978 source
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
Premisecitation§ DiscussionCoculturing endothelial cells with primary glial cultures results in marked changes of several endothelial parameters, suggesting that several structural and functional characteristics of cerebral capillaries are determined by surrounding astrocytes.
“It is well established that coculturing ECs with primary glial cultures results in marked changes of several endothelial parameters, which suggests that several structural and functional charac- teristics of cerebral capillaries are determined by the sur- rounding astrocytes 0o6, 1992).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites 0o6, 1992
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
It may state two separate claims as one.
Interpretationreasoning§ DiscussionThe occurrence of the LDL receptor on brain capillary endothelial cells at confluence and in the presence of a high concentration of lipoproteins could be explained not only by the originality of the cell type used but also by local control of astrocytes.
“the occurrence of the LDL receptor on brain capillary endothelial cells at confluence and in the presence of a high concentration of lipoproteins could be explained not only by the originality of the cell type used (brain capillary en- dothelial cells), but also by the local control of astrocytes.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Interpretationnone given§ DiscussionAUF liberation is specific and occurs only with cocultured brain capillary endothelial cells and astrocytes.
“AUF liberation is specific and occurs only with coculmred brain capillary endothelial cells and astrocytes.”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Premisecitation§ DiscussionEstrada et al. showed that a peptide with molecular weight greater than 50,000 derived from cerebral capillary endothelial cells could be involved in local signaling between cell types that control new vessel formation in development.
“Estrada et al. (1990) have shown that a peptide with molecu- lar weight >50000 derived from cerebral capillary ECs could be involved in the local signaling between cell types that control new vessel formation in development (i.e., brain capillary ECs and astrocytes).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Estrada et al. (1990) source
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
Study design and conductcitation§ Materials and MethodsAstrocyte cultures were characterized with GFAP, and >95% of the population was GFAP positive.
“The astrocytes were characterized with glial flbtiUary acidic protein (GFAP), and >95 % of the population was GFAP positive (Dehouck et al., 1990/,).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Dehouck et al., 1990b
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
It may state two separate claims as one.
Interpretationown data§ AbstractThe upregulation is specific: substituting astrocytes with smooth muscle cells or brain endothelium with endothelium from the aorta or the adrenal cortex does not enhance luminal LDL receptor expression on endothelial cells.
“Substituting astrocytes with smooth muscle cells or brain endothelium with endothelium from the aorta or the adrenal cortex did not enhance the luminal LDL receptor expression on endothelial cells, demonstrating the specificity of the interactions.”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper may give no reason why it holds.
Study design and conductnone given§ ResultsThe culture of brain capillary endothelial cells is a pure endothelial cell population without contamination by pericytes.
“This culture is a pure en- dothelial cell population without contaminationby pericytes.”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Premisecitation§ AbstractBrain capillary endothelial cells in vivo express an LDL receptor, in contrast to large vessel endothelial cells where LDL receptors are downregulated.
“In contrast to the endothelial cells in large vessels where LDL receptors are downregulated, brain capillary endothelial cells in vivo express an LDL receptor.”
Quote in the paperSubstantial claim0 of 3 sources checkedProbably not a substantial claim. The paper’s conclusions may not depend on it.
Premisecitation§ DiscussionPitas et al. proposed a model for cholesterol transport and homeostasis within the central nervous system.
“Pitas et al. (1987) have proposed a model for cholesterol transport and homeostasis within the central nervous sys- tem.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Pitas et al. (1987) source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
Premisecitation§ IntroductionLDL receptors are regulated by a feedback mechanism responsive to the availability of LDL in the surrounding medium.
“These receptors appear to be regulated by a feedback mechanism responsive to the avail- ability of LDL in the surrounding medium. These authors have suggested that LDL suppresses the synthesis of new receptor sites.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Brown et al., 1981 source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
Premisecitation§ DiscussionAngiogenin was mitogenic only for brain capillary endothelial cells.
“we showed that an- giogenin was mitogenic only for brain capillary ECs (Cha- moux et al., 1991).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Chamoux et al., 1991 source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
Premisecitation§ DiscussionCancilla and DeBault showed that the proximity in vitro of astrocytes enhances the uptake of neutral amino acids by endothelial cells.
“Cancilla and DeBault (1983) have already shown that the proximity in vitro of astrocytes enhances the uptake of neutral amino acids by ECs.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Cancilla and DeBault (1983) source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
Premisecitation§ DiscussionApolipoprotein E secreted by astrocytes within the brain transports and redistributes cholesterol via brain interstitial fluid to cells that require cholesterol and express apolipoprotein B,E (LDL) receptors.
“Apolipoprotein E, secreted by astrocytes within the brain, transports and redistributes cholesterol via brain in- terstitial fluid to cells that require cholesterol and express apolipoprotein B,E (LDL) receptors (Hofman et al., 1987).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Hofman et al., 1987
Couldn’t be matched to a paper in Crossref, so it can’t be checked.
The paper relies on this without support.
Aortic endothelial cells and smooth muscle cells have no intracellular pool of LDL receptor.
“aortic ECs and smooth muscle cells have no intracellular pool of LDL receptor”
The paper relies on this without support.
Astrocytes are capable of influencing the differentiation of brain endothelial cells in culture, as they are in vivo.
“It is well known that astrocytes are capable of influencingthe differentiationofbrain ECs in culture, as they are in vivo.”
The paper relies on this without support.
The direct action of LPDS on endothelial cells is well known, and lipoprotein receptor activity of endothelial cells is upregulated by exposure to LPDS after a minimum of 24 h.
“the direct action of LPDS on endothelial cells is very well known, and lipoprotein receptor activity of EC is up- regulated by exposure to LPDS after a minimum of 24 h.”
The paper relies on this without support.
Cycloheximide inhibits peptidyl transferase on the eukaryotic large ribosomal subunit and therefore protein synthesis in the cell.
“Cycloheximide, known to inhibit peptidyl transferase on eu- karyiotic large ribosomal subunit, and therefore protein syn- thesis in the cell”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Incubation with LDL alters astrocyte morphology.
“Moreover, incubation with LDL has been shown to alter astrocyte morphology, although the specific consequences and mechanisms by which LDL cholesterol affects astrocytes remain incompletely understood (Dehouck et al. 1994; Engel et al. 2019; Pitas et al. 1987).”
From LDL Cholesterol Modulates Astrocyte Metabolism, Lipid Handling, and Morphology: Evidence From In Vitro and In Vivo Models (2026) · cites this paper as Dehouck et al. 1994
The section “Cholesterol Content and Binding of LDL on Astrocytes” reports changes in LDL binding and cholesterol content after incubation in lipoprotein-deficient serum, not changes in astrocyte morphology after incubation with LDL. Searches for astrocyte morphology, shape, and LDL incubation found no passage addressing the claimed morphological effect. (LLM, conf=0.76)
Experimental — accuracy not yet measuredThe specific consequences and mechanisms by which LDL cholesterol affects astrocytes remain incompletely understood.
“Moreover, incubation with LDL has been shown to alter astrocyte morphology, although the specific consequences and mechanisms by which LDL cholesterol affects astrocytes remain incompletely understood (Dehouck et al. 1994; Engel et al. 2019; Pitas et al. 1987).”
From LDL Cholesterol Modulates Astrocyte Metabolism, Lipid Handling, and Morphology: Evidence From In Vitro and In Vivo Models (2026) · cites this paper as Dehouck et al. 1994
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Metadata
- Authors
- Dehouck, B., Dehouck, M. P., Fruchart, J. C., & Cecchelli, R.
- Affiliations
- Inserm (FR)
- ORCID
- Dehouck, M P
- Venue
- The Journal of cell biology
- Publisher
- Rockefeller University Press
- Published
- 1994-07-15
- Volume
- 126
- Issue
- 2
- Pages
- 465-473
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2200038
- OpenAlex
- W2159464926
- Semantic Scholar
- cf88aa0075b09115170892dbefe55b2f59dfa9db
- Cited by
- 240
- References
- 34
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 3 · 2023: 9 · 2022: 7 · 2021: 6 · 2020: 8 · 2019: 3 · 2018: 5 · 2017: 10 · 2016: 7 · 2015: 7 · 2014: 11 · 2013: 13 · 2012: 7
- FWCI
- 7.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- LDL receptor, blood-brain barrier, brain microvascular endothelial cells, astrocytes, LDL binding, soluble factors, receptor up-regulation, cell differentiation
- MeSH terms
- Adrenal Cortex, Animals, Aorta, Astrocytes, Binding Sites, Biological Factors, Blood-Brain Barrier, Brain, Capillaries, Cattle, Cell Communication, Cholesterol, Endothelium, Vascular, Kinetics, Lipoproteins, LDL, Muscle, Smooth, Receptors, LDL, Up-Regulation, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-11-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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