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R E Pitas

Publications and source records attributed to R E Pitas.

At least 19 recordsLinked to original sources
PubMed1997

Apolipoprotein E4 (ApoE4) but not ApoE3 or ApoE2 potentiates beta-amyloid protein activation of complement in vitro.

Apolipoprotein E4 (ApoE4) increases the risk of late-onset Alzheimer's disease (AD). It binds tightly to beta-amyloid protein (A beta), which is known to activate the classical complement pathway in vitro. Since complement activation is a possible mechanism for promoting inflammation in AD, we tested, utilizing ELISA techniques, whether the various isoforms of ApoE could influence A beta complement activation, or could themselves activate the pathway. A beta applied alone to ELISA plate wells at concentrations of 100-500 ng showed a linear increase in ability to activate serum complement, but all the ApoE isoproteins were inactive. When 200 or 430 ng of A beta were plated and then exposed to solutions of 100-200 ng of ApoE2, ApoE3, ApoE4 or bovine serum albumin (BSA), only ApoE4 significantly enhanced the activation. This ApoE4-specific enhancement of complement activation by A beta may relate to its role in increasing the risk of late-onset AD.

Alzheimer Disease↗
PubMed1996

Disruption of the acyl-CoA:cholesterol acyltransferase gene in mice: evidence suggesting multiple cholesterol esterification enzymes in mammals.

The microsomal enzyme acyl-CoA:cholesterol acyltransferase (ACAT; EC 2.3.1.26) catalyzes the esterification of cellular cholesterol with fatty acids to form cholesterol esters. ACAT activity is found in many tissues, including macrophages, the adrenal glands, and the liver. In macrophages, ACAT is thought to participate in foam cell formation and thereby to contribute to atherosclerotic lesion development. Disruption of the gene for ACAT (Acact) in mice resulted in decreased cholesterol esterification in ACAT-deficient fibroblasts and adrenal membranes, and markedly reduced cholesterol ester levels in adrenal glands and peritoneal macrophages; the latter finding will be useful in testing the role of ACAT and macrophage foam cell formation in atherosclerosis. In contrast, the livers of ACAT-deficient mice contained substantial amounts of cholesterol esters and exhibited no reduction in cholesterol esterification activity. These tissue-specific reductions in cholesterol esterification provide evidence that in mammals this process involves more than one form of esterification enzyme.

Adrenal Glands↗
PubMed1996

Apolipoprotein E. Structure, function, and possible roles in Alzheimer's disease.

Apolipoprotein (apo) E is associated with the two characteristic neuropathologic lesions of Alzheimer's disease--extracellular neuritic plaques representing deposits of amyloid beta (A beta) peptide and intracellular neurofibrillary tangles representing filaments of a microtubule-associated protein called tau. Incubation of the apoE4 isoform with the A beta peptide in vitro results in the formation of a dense, stable network of very long monofibrils, while incubation of apoE3 with the A beta peptide results in the formation of a less dense, less stable network. The more complex nature of the plaques formed with the A beta peptide in the presence of apoE4 in vivo may impair the normal clearance process and enhance plaque formation. Alternatively or additionally, apoE may alter the cytoskeletal structure and function and, under certain conditions, may promote the formation of the neurofibrillary tangles. Our studies have demonstrated that apoE3 and apoE4 exert differential effects on neuronal growth (i.e., neurite extension and branching) in vitro. When combined with a source of lipid, apoE3 stimulated neurite extension in peripheral nervous system neurons (dorsal root ganglia), whereas apoE4 inhibited it. Similar results were obtained with central nervous system neurons (murine neuroblastoma Neuro-2a cells). Addition of free apoE3 or apoE4 without beta-VLDL had no effect on neurite outgrowth. There was also differential accumulation of apoE3 and apoE4 by the neuroblastoma cells: apoE3 accumulated within cell bodies and neurites to a greater extent than apoE4. Thus, apoE3 may facilitate cytoskeletal activity, whereas apoE4 may inhibit it, which would be detrimental during synaptic remodeling.

Alzheimer Disease↗
PubMed1995

Stable expression and secretion of apolipoproteins E3 and E4 in mouse neuroblastoma cells produces differential effects on neurite outgrowth.

Previously, we demonstrated in cultured dorsal root ganglion neurons that, in the presence of beta-migrating very low density lipoproteins (beta-VLDL), apolipoprotein (apo) E4, but not apoE3, suppresses neurite outgrowth. In the current studies, murine neuroblastoma cells (Neuro-2a) were stably transfected with human apoE3 or apoE4 cDNA, and the effect on neurite outgrowth was examined. The stably transfected cells secreted nanogram quantities of apoE (44-89 ng/mg of cell protein in 48 h). In the absence of lipoproteins, neurite outgrowth was similar in the apoE3- and apoE4-secreting cells. The apoE4-secreting cells, when incubated with beta-VLDL, VLDL, cerebrospinal fluid lipoproteins (d < 1.21 g/ml), or with triglyceride/phospholipid (2.7:1 (w/w)) emulsions, showed a reduction in the number of neurites/cell, a decrease in neurite branching, and an inhibition of neurite extension, whereas in the apoE3-secreting cells in the presence of a lipid source, neurite extension was increased. Uptake of beta-VLDL occurred to a similar extent in both the apoE3- and apoE4-secreting cells. With low density lipoproteins or with dimyristoylphosphatidylcholine emulsions, either alone or complexed with cholesterol, no differential effect on neurite outgrowth was observed. A slight differential effect was observed with apoE-containing high density lipoproteins. The differential effect of apoE3 and apoE4 in the presence of beta-VLDL was blocked by incubation of the cells with heparinase and chlorate, with lactoferrin, or with receptor-associated protein, all of which prevent the uptake of lipoproteins by the low density lipoprotein receptor-related protein (LRP). The data suggest that the secreted and/or cell surface-bound apoE interact with the lipoproteins and facilitate their internalization via the heparan sulfate proteoglycan-LRP pathway. The mechanism by which apoE3 and apoE4 exert differential effects on neurite outgrowth remains speculative. However, the data suggest that apoE4, which has been shown to be associated with late onset familial and sporadic Alzheimer's disease, may inhibit neuronal remodeling and contribute to the progression of the disease.

Alzheimer Disease↗
PubMed1995

Low density lipoprotein receptor-related protein mediates apolipoprotein E-dependent neurite outgrowth in a central nervous system-derived neuronal cell line.

The epsilon 4 allele of apolipoprotein E (apoE) is a major risk factor for Alzheimer disease, suggesting that apoE may directly influence neurons in the aging brain. Recent data suggest that apoE-containing lipoproteins can influence neurite outgrowth in an isoform-specific fashion. The neuronal mediators of apoE effects have not been clarified. We show here that in a central nervous system-derived neuronal cell line, apoE3 but not apoE4 increases neurite extension. The effect of apoE3 was blocked at low nanomolar concentrations by purified 39-kDa protein that regulates ligand binding to the low density lipoprotein receptor-related protein (LRP). Anti-LRP antibody also completely abolished the neurite-promoting effect of apoE3. Understanding isoform-specific cell biological processes mediated by apoE-LRP interactions in central nervous system neurons may provide insight into Alzheimer disease pathogenesis.

Apolipoprotein E3↗
PubMed1995

Synergistic effects of growth factors on the regulation of smooth muscle cell scavenger receptor activity.

Rabbit smooth muscle cells (SMC) express types I and II scavenger receptors (ScR) that are up-regulated by platelet secretion products. In the current studies we investigated the effect of growth factors secreted by platelets on ScR activity in rabbit and human SMC. Platelet-derived growth factor (PDGF BB) and transforming growth factor beta 1 (TGF-beta 1) at 10 ng/ml increased ScR activity in rabbit SMC (by approximately 4- and 2-fold, respectively) but not in human SMC. Epidermal growth factor (EGF) or insulin-like growth factor I (IGF-I) alone had little effect on SMC ScR activity. The growth factors had synergistic effects on ScR activity and on types I and II ScR mRNA expression. In rabbit SMC, PDGF BB, EGF, and TGF-beta 1 together stimulated ScR activity 12-fold. In human SMC, EGF and TGF-beta 1, together with either IGF-I or PDGF BB, stimulated receptor activity approximately 7-fold. Growth factor-mediated induction of ScR activity in rabbit and human SMC was blocked by the tyrosine kinase inhibitor tyrphostin 47, whereas the induction of ScR activity in rabbit but not human SMC was blocked by the protein kinase C inhibitor MDL.29,152. Studies using neutralizing antibodies demonstrated that TGF-beta 1 is the predominant factor in in vitro preparations of platelet secretory products which regulates ScR activity. The growth factors that act synergistically in regulating ScR activity in vitro are all present in atherosclerotic lesions, where they are produced by macrophages, endothelial cells, SMC, and platelets. The data suggest that these growth factors may regulate ScR activity in SMC in vivo and contribute to foam cell formation.

Animals↗
PubMed1995

The inhibitory effect of apolipoprotein E4 on neurite outgrowth is associated with microtubule depolymerization.

Evidence is presented for the differential effects of two isoforms of apolipoprotein (apo) E, apoE3 and apoE4, on neurite outgrowth and on the cytoskeleton of neuronal cells (Neuro-2a) in culture. In the presence of a lipid source, apoE3 enhances and apoE4 inhibits neurite outgrowth. Immunocytochemical studies demonstrate that there is a higher concentration of apoE3 than apoE4 in both the cell bodies and neurites. Cells treated with apoE4 showed fewer microtubules and a greatly reduced ratio of polymerized to monomeric tubulin than did cells treated with apoE3. The effect of apoE4 on depolymerization of microtubules was shown by biochemical, immunocytochemical, and ultrastructural studies. The depolymerization of microtubules and the inhibition of neurite outgrowth associated with apoE4 suggest a mechanism whereby apoE4, which has been linked to the pathogenesis of Alzheimer's disease, may prevent normal neuronal remodeling from occurring later in life, when this neurodegenerative disorder develops.

Actins↗
PubMed1995

Macrophage-specific expression of human apolipoprotein E reduces atherosclerosis in hypercholesterolemic apolipoprotein E-null mice.

apoE deficiency causes hyperlipidemia and premature atherosclerosis. To determine if macrophage-specific expression of apoE would decrease the extent of atherosclerosis, we expressed human apoE in macrophages of apoE-null mice (apoE-/-) and assessed the effect on lipid accumulation in cells of the arterial wall. Macrophage-specific expression of human apoE in normal mice was obtained by use of the visna virus LTR. These animals were bred with apoE-/- mice to produce animals hemizygous for expression of human apoE in macrophages in the absence of murine apoE (apoE-/-,hTgE+/0). Low levels of human apoE mRNA were present in liver and spleen and high levels in lung and peritoneal macrophages. Human apoE was secreted by peritoneal macrophages and was detected in Kupffer cells of the liver. Human apoE in the plasma of apoE-/-,hTgE+/0 mice (n = 30) was inversely correlated (P < 0.005) with the plasma cholesterol concentration. After 15 wk on a normal chow diet, atherosclerosis was assessed in apoE-/-,hTgE+/0 animals and in apoE-/-,hTgE0/0 littermates matched for plasma cholesterol level (approximately 450 mg/dl) and lipoprotein profile. There was significantly less atherosclerosis in both the aortic sinus and in the proximal aorta (P < 0.0001) in the animals expressing the human apoE transgene. In apo-E-/-,hTgE+/0 animals, which had detectable atherosclerotic lesions, human apoE was detected in the secretory apparatus of macrophage-derived foam cells in the arterial wall. The data demonstrate that expression of apoE by macrophages is antiatherogenic even in the presence of high levels of atherogenic lipoproteins. The data suggest that apoE prevents atherosclerosis by promoting cholesterol efflux from cells of the arterial wall.

Animals↗
PubMed1995

A genetic model for absent chylomicron formation: mice producing apolipoprotein B in the liver, but not in the intestine.

The formation of chylomicrons by the intestine is important for the absorption of dietary fats and fat-soluble vitamins (e.g., retinol, alpha-tocopherol). Apo B plays an essential structural role in the formation of chylomicrons in the intestine as well as the VLDL in the liver. We have developed genetically modified mice that express apo B in the liver but not in the intestine. By electron microscopy, the enterocytes of these mice lacked nascent chylomicrons in the endoplasmic reticulum and Golgi apparatus. Because these mice could not form chylomicrons, the intestinal villus enterocytes were massively engorged with fat, which was contained in cytosolic lipid droplets. These mice absorbed D-xylose normally, but there was virtually no absorption of retinol palmitate or cholesterol. The levels of alpha-tocopherol in the plasma were extremely low. Of note, the absence of chylomicron synthesis in the intestine did not appear to have a significant effect on the plasma levels of the apo B-containing lipoproteins produced by the liver. The mice lacking intestinal apo B expression represent the first genetic model of defective absorption of fats and fat-soluble vitamins and provide a useful animal model for studying nutrition and lipoprotein metabolism.

Animals↗
PubMed1994

Differential effects of apolipoproteins E3 and E4 on neuronal growth in vitro.

Apolipoprotein E4 (apoE4), one of the three common isoforms of apoE, has been implicated in Alzheimer's disease. The effects of apoE on neuronal growth were determined in cultures of dorsal root ganglion neurons. In the presence of beta-migrating very low density lipoproteins (beta-VLDL), apoE3 increased neurite outgrowth, whereas apoE4 decreased outgrowth. The effects of apoE3 or apoE4 in the presence of beta-VLDL were prevented by incubation with a monoclonal antibody to apoE or by reductive methylation of apoE, both of which block the ability of apoE to interact with lipoprotein receptors. The data suggest that receptor-mediated binding or internalization (or both) of apoE-enriched beta-VLDL leads to isoform-specific differences in interactions with cellular proteins that affect neurite outgrowth.

Animals↗
PubMed1994

Isolation and characterization of a platelet-derived macrophage-binding proteoglycan.

A macromolecule in human platelet secretory products was demonstrated previously to inhibit the binding and uptake of acetoacetylated (AcAc) low density lipoproteins (LDL) by scavenger receptors on mouse peritoneal macrophages. In the current study, this macromolecule was purified to apparent homogeneity by DEAE-Sephacel chromatography, Sephacryl S-300 chromatography, and sucrose gradient centrifugation. SDS-polyacrylamide gel electrophoresis revealed a single band with an apparent molecular mass of approximately 120 kDa. Chemical analysis indicated that the macromolecule (designated platelet-derived macrophage-binding proteoglycan (PDMBP)) was a chondroitin 4-sulfate proteoglycan with an approximately 32-kDa core protein. A polyclonal antibody produced against this proteoglycan identified only PDMBP on Western blots of platelet secretory products and removed all ability of these products to inhibit the binding of AcAc LDL to macrophages. Treatment of purified PDMBP with protease or chondroitinase AC or ABC abolished the ability of the proteoglycan to inhibit the binding of AcAc LDL to macrophages. Binding studies using radiolabeled PDMBP demonstrated that the proteoglycan bound directly to the macrophage cell surface and was competitively inhibited by AcAc LDL, acetyl-LDL, fucoidin, and unlabeled PDMBP. PDMBP inhibited binding of 125I-labeled AcAc LDL to macrophages but had no effect on binding to endothelial cells. The finding that PDMBP binds to the scavenger receptor on macrophages suggests a mechanism for the inhibition of foam cell formation and suggests that the receptor could be involved in the plasma clearance of chondroitin sulfate proteoglycans.

Amino Acids↗
PubMed1993

Oxidized low density lipoproteins bind to the scavenger receptor expressed by rabbit smooth muscle cells and macrophages.

We have previously demonstrated that the acetylated low density lipoprotein (LDL), or scavenger, receptor expressed by rabbit smooth muscle cells (SMCs) is regulated. Phorbol ester treatment of the cells increased the number of scavenger receptors expressed and the metabolism of acetoacetylated (AcAc) LDL. The current studies examined the interaction of oxidized (Ox) LDL with the rabbit scavenger receptor. The internalization and degradation of both Ox-LDL and AcAc-LDL were increased to a similar extent by phorbol ester treatment of the SMCs. In cross-competition experiments, both Ox-LDL and AcAc-LDL competed equally for the degradation of 125I-Ox-LDL, suggesting that there is no independent receptor for Ox-LDL on these cells. In contrast, only AcAc-LDL competed totally for the degradation of 125I-AcAc-LDL. Similar results were obtained in cross-competition experiments with rabbit macrophages. To determine whether these data were consistent with the binding of both ligands to a single receptor, competition studies were conducted in Chinese hamster ovary fibroblasts transfected with the bovine scavenger receptor. After transfection, the metabolism of both AcAc-LDL and Ox-LDL was increased, in agreement with the previous data from other investigators, and cross-competition studies yielded essentially identical results to those obtained in the SMCs and macrophages. Northern blot analysis with an antisense rabbit scavenger receptor probe detected the same mRNA species in total RNA from rabbit macrophages and SMCs and showed that scavenger receptor mRNA increased dramatically after phorbol ester treatment of SMCs. The probe also detected bovine scavenger receptor mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Dominant negative mutations of the scavenger receptor. Native receptor inactivation by expression of truncated variants.

The bovine scavenger receptor was truncated at amino acid 266 or 310 to delete either all or part, respectively, of the collagen-like domain. The truncated receptors were inactive in the binding and internalization of acetyl (Ac) low density lipoprotein (LDL). Coexpression of truncated receptor with the native receptor dramatically reduced the percentage of cells internalizing fluorescently labeled Ac LDL, compared with cells expressing the native receptor alone. The mutant truncated at amino acid 266 was most effective in receptor inactivation, resulting in a 42% or 80% decrease in the percentage of cells expressing active receptor when transfected in a 1:1 or 1:2 molar ratio (native:mutant), respectively, with native receptor. Degradation of 125I-Ac LDL was reduced up to 90% when the native and truncated mutant receptors were coexpressed. Scavenger receptor inhibition was specific because the activity of the LDL receptor was not altered. Transient transfection of the mouse macrophage cell line P388D1 with truncated scavenger receptor resulted in a 65% decrease in the uptake and degradation of Ac LDL but did not decrease the degradation of beta-migrating very low density lipoprotein, which is LDL receptor-mediated. These results demonstrate that expression of truncated bovine scavenger receptor inactivates both the native bovine and murine scavenger receptors, producing a dominant negative phenotype in vitro.

Animals↗
PubMed1992

Evidence that the scavenger receptor is not involved in the uptake of negatively charged liposomes by cells.

Scavenger receptors have a broad ligand specificity, ranging from modified low-density lipoproteins to a variety of high-molecular-weight poly-anions. A recent report by Nishikawa et al. (J. Biol. Chem. (1990) 265, 5226-5231) suggested that this receptor is also involved in the binding and endocytosis of liposomes containing negatively charged phospholipids. The mechanism by which liposomes are taken up by cells is of interest because liposomes are promising versatile carriers for macromolecules and drugs both in vitro and in vivo. In this report, we re-examine the role of the scavenger receptor in the uptake of liposomes using both Chinese hamster ovary cells transfected with the type I or type II bovine scavenger receptor, and smooth muscle cells induced to increase scavenger receptor expression by phorbol ester treatment. Expression of both types of scavenger receptors by Chinese hamster ovary cells induced an increase in the uptake of chemically modified low-density lipoproteins, but not the uptake of negatively charged liposomes. In smooth muscle cells treated with phorbol ester, scavenger receptor expression was upregulated and the uptake of chemically modified low-density lipoproteins was enhanced dramatically, but there was no effect on the uptake of negatively charged liposomes. We conclude that the existing evidence does not support the suggestion that the scavenger receptor is involved in the uptake of anionic liposomes by cells.

Animals↗
PubMed1992

Regulation of endothelial cell protein C activation by native and oxidized low density lipoprotein.

The effects of native LDL and Ox-LDL and HDL on endothelial cell protein C activation were examined. Ox-LDL, which is postulated to contribute to cardiovascular disease, markedly suppressed activation of protein C, an important vascular anticoagulant activity. This effect was seen with both human venous and arterial endothelial cells. Endothelial cells modified LDL to a form that reduced protein C activation, an effect prevented by the anti-oxidant, probucol. Endothelial cells are known to express the acetyl LDL (scavenger) receptor, which binds chemically modified and Ox-LDL. The effect of Ox-LDL on protein C activation does not appear to result from uptake via the acetyl LDL receptor, since a known scavenger receptor antagonist (fucoidin) did not inhibit the oxidized LDL effect. In contrast to the results with Ox-LDL, native LDL and both native and oxidized HDL increased protein C activation. These data indicate that native and modified lipoproteins regulate blood coagulation by affecting vascular anticoagulant activity and suggest mechanisms that may link modified lipoproteins with both vascular disease and thrombosis.

Cells, Cultured↗
PubMed1992

Further characterization of the acetyl LDL (scavenger) receptor expressed by rabbit smooth muscle cells and fibroblasts.

We have previously demonstrated that the acetyl low density lipoprotein (LDL), or scavenger, receptor is expressed by rabbit smooth muscle cells (SMCs) and fibroblasts. Moreover, receptor activity in rabbit fibroblasts was regulated over a wide range by preincubating the cells with secretion products from human platelets or with phorbol esters. The current studies were undertaken to examine the regulation of receptor expression in rabbit SMCs, to characterize further the receptor expressed by rabbit SMCs and fibroblasts, and to determine whether incubating these cells with chemically modified lipoproteins would lead to foam cell formation. Receptor activity was increased fivefold in rabbit SMCs by preincubation with platelet secretion products and nine- to 20-fold by preincubation with phorbol esters or mezerein, a non-phorbol activator of protein kinase C. The phorbol ester-induced increase in receptor activity was due to an increased mass of scavenger receptor as determined by both ligand blots and immunoblots of membrane proteins from these cells. The immunoblotting studies suggest that the SMC scavenger receptor activity is due to type I or type II scavenger receptors. The scavenger receptor expressed by phorbol ester-treated rabbit SMCs and fibroblasts bound chemically modified LDL with an order-of-magnitude higher affinity (Kd 5.1 x 10(-10) M) than did the scavenger receptor expressed by mouse peritoneal macrophages (Kd 4.1 x 10(-9) M), whereas rabbit macrophages bound chemically modified LDL with intermediate affinity (Kd 1.0 x 10(-9) M). Both the phorbol ester-stimulated rabbit fibroblasts and SMCs expressed 10-30% as many receptors per cell as did mouse peritoneal macrophages. Consistent with the difference in the number of receptors, uptake of the chemically modified LDL at 37 degrees C by SMCs led to approximately 25% as much lysosomal degradation and stimulation of cholesterol esterification as in mouse peritoneal macrophages. Incubation of phorbol ester-treated rabbit fibroblasts or SMCs with chemically modified LDL (50 micrograms/ml) for 24 or 48 hours, respectively, resulted in a threefold increase in total cholesterol and a 15-fold increase in cholesteryl ester within the cells. These studies suggest that the scavenger receptor-mediated uptake of modified lipoproteins may contribute to the formation of SMC foam cells in atherosclerotic lesions.

Animals↗
PubMed1992

Effects of apolipoprotein E, beta-very low density lipoproteins, and cholesterol on the extension of neurites by rabbit dorsal root ganglion neurons in vitro.

Previous studies suggest that during nerve regeneration apoE acts as a lipid transport protein that assists in the rapid initial extension of axons and then in their myelination. To determine whether apoE and/or apoE-containing lipoproteins can modulate axon growth, we assessed their effect on the out-growth of neurites from neurons in mixed cultures of fetal rabbit dorsal root ganglion cells in vitro. Incubation with beta-very low density lipoprotein (beta-VLDL) particles, which are rich in apoE and cholesterol, increased neurite outgrowth and branching. Unesterified cholesterol added to the cultures had a similar, but less pronounced, effect. These data suggest that cholesterol might be the component responsible for the enhanced neurite growth. In contrast, purified, lipid-free apoE added to the cultures reduced neurite branching. Neurite branching was also reduced when purified apoE was added along with beta-VLDL or cholesterol; however, the striking finding was that under these conditions the neurites extended farther from the neuronal cell body. Dorsal root ganglion cells were examined for the presence of receptors for native and apoE-enriched beta-VLDL. Immunocytochemistry, ligand blots, 45Ca2+ blots, and studies of the interaction of the cells with fluorescent lipoproteins provided evidence of two types of receptors for apoE-containing lipoproteins on neurons: the low density lipoprotein (LDL) receptor, which binds native beta-VLDL, and the LDL receptor-related protein, which binds apoE-enriched beta-VLDL. These findings indicate that apoE may play two complementary roles in neurite outgrowth. When complexed with lipoproteins, apoE stimulates neurite growth by the receptor-mediated delivery of cholesterol and perhaps other components necessary for neurite outgrowth. When apoE as a free protein is added together with apoE-containing lipoproteins, apoE decreases neurite branching and promotes neurite extension away from the cell body. These actions, which would be complementary in promoting target-directed nerve growth in vivo, provide the first direct evidence that apoE and apoE-containing lipoproteins can modulate the outgrowth of neuronal processes.

Animals↗