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PubMed2004

Partitioning of dual-lipidated peptides into membrane microdomains: lipid sorting vs peptide aggregation.

The lateral membrane organization and phase behavior of the lipid mixture DMPC(di-C(14))/DSPC(di-C(18))/cholesterol (0-33 mol %) with and without an incorporated fluorescence-labeled palmitoyl/farnesyl dual-lipidated peptide, BODIPY-Gly-Cys(Pal)-Met-Gly-Leu-Pro-Cys(Far)-OMe, which represents a membrane recognition model system for Ras proteins, was studied by two-photon excitation fluorescence microscopy. Measurements were performed on giant unilamellar vesicles (GUVs) over a large temperature range, ranging from 30 to 80 degrees C to cover different lipid phase states (all-gel, fluid/gel, liquid-ordered, all-fluid). At temperatures where the fluid-gel coexistence region of the pure binary phospholipid system occurs, large-scale concentration fluctuations appear. Incorporation of cholesterol levels up to 33 mol % leads to a significant increase of conformational order in the membrane system and a reduction of large domain structures. Adding the peptide leads to dramatic changes in the lateral organization of the membrane. With cholesterol present, a phase separation is induced by a lipid sorting mechanism owing to the high affinity of the lipidated peptide to a fluid, DMPC-rich environment. This phase separation leads to the formation of peptide-containing domains with high fluorescence intensity that become progressively smaller with decreasing temperature. As a result, the local concentration of the peptide increases steadily within the confines of the shrinking domains. At the lowest temperatures, where the acyl-chain order parameter of the membrane has already drastically increased and the membrane achieves a liquid-ordered character, an efficient lipid sorting mechanism is no longer supported and aggregation of the peptide into small clusters prevails. We can conclude that palmitoyl/farnesyl dual-lipidated peptides do not associate with liquid-ordered or gel-like domains in phase-separated bilayer membranes. In particular, the study shows the interesting ability of the peptide to induce formation of fluid microdomains at physiologically relevant cholesterol concentrations, and this effect very much depends on the concentration of fluid vs ordered lipid molecules.

Cholesterol↗

PubMed2005

Multicomponent cationic lipid-DNA complex formation: role of lipid mixing.

Multicomponent cationic lipid-DNA complexes (lipoplexes) were prepared by adding linear DNA to mixed lipid dispersions containing two populations of binary cationic liposomes and characterized by means of small angle X-ray scattering (SAXS). Four kinds of cationic liposomes were used. The first binary lipid mixture was made of the cationic lipid (3'[N-(N',N'-dimethylaminoethane)-carbamoyl]cholesterol (DC-Chol) and the neutral helper lipid dioleoylphosphocholine (DOPC) (DC-Chol/DOPC liposomes), the second one of the cationic 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and the neutral dioleoylphosphatidylethanolamine (DOPE) (DOTAP/DOPE liposomes), the third one of DC-Chol and DOPE (DC-Chol/DOPE liposomes), and the fourth one of DOTAP and DOPC (DOTAP/DOPC liposomes). Upon DNA-induced fusion of liposomes, large lipid mixing at the molecular level occurs. As a result, highly organized mixed lipoplexes spontaneously form with membrane properties intermediate between those of starting liposomes. By varying the composition of lipid dispersions, different DNA packing density regimes can also be achieved. Furthermore, occurring lipid mixing was found to induce hexagonal to lamellar phase transition in DOTAP/DOPE membranes. Molecular mechanisms underlying experimental findings are discussed.

Cations↗

PubMed1979

Lipid peroxidation of the microsomal fraction and extracted microsomal lipids from DAB-induced hepatomas.

NADPH- and ascorbic acid-induced microsomal lipid peroxidation was almost absent in subcutaneously implanted DAB-induced hepatomas D23, D30 and D192A, and present at greatly reduced levels in DAB-induced primary hepatomas when compared with normal liver controls. Fatty acid analysis of the microsomal lipid from passaged tumours demonstrated adequate levels of substrate in the phospholipid fractions to support lipid peroxidation. Lipid extracted from hepatoma microsomal fractions was shown to undergo ascorbic acid-induced lipid peroxidation, but to a lesser extent that the corresponding liver extract. This may be partially explained by a decrease in the phospholipid content of hepatoma microsomal membranes. However, phospholipid extracted from microsomal fractions of hepatoma and liver supported lipid peroxidation to a similar extent. The possible role of the non-lipid component of the membrane in the process of lipid peroxidation is discussed.

Animals↗

PubMed1969

Lipid peroxide formation in microsomes. Relationship of hydroxylation to lipid peroxide formation.

1. Aminopyrine strongly inhibits NADPH-induced lipid peroxide formation in rat liver microsomes, but ascorbate-induced peroxidation is inhibited to a smaller extent. 2. Aminopyrine oxidation is stimulated by Mg(2+) but inhibited by Ca(2+). Concentrated solutions (10mm) of iron-chelating agents inhibit aminopyrine oxidation, but the more dilute solutions (0.5mm) of chelators that block lipid peroxide formation do not inhibit aminopyrine oxidation. Microsomes prepared from sucrose-EDTA homogenates rapidly oxidize aminopyrine, but do not form lipid peroxide when incubated with ascorbate or NADPH. 3. Aminopyrine oxidation is strongly inhibited by p-chloromercuribenzoate, less by iodoacetamide and weakly by N-ethylmaleimide. The site of action of these compounds is considered to be a ferredoxin-type protein. GSH and cysteine also inhibit. 4. Other drugs oxidized by microsomes such as caffeine, phenobarbitone and hexobarbitone had either no or little effect on lipid peroxide formation, but codeine inhibited. 5. Most aliphatic hydrocarbons, alcohols, ketones and aldehydes did not affect lipid peroxide formation, but chloroform and carbon tetrachloride inhibited. 6. Many aromatic compounds inhibited lipid peroxide formation. Only aromatic acids were without any effect and phenols and amines were very strong inhibitors. 7. Induction of lipid peroxide formation in microsomes by incubation with ascorbate or NADPH or by treatment with ionizing radiation leads to a sharp decline in the ability of microsomes to oxidize aminopyrine or hydroxylate aniline. 8. It is considered that the two processes of hydroxylation and lipid peroxide formation are closely linked in microsomes. They probably depend on the same electron-transport chain, and peroxide formation, which involves membrane disintegration, may be part of the normal membrane remodelling process.

Aminopyrine↗

PubMed1993

Lipid advanced glycosylation: pathway for lipid oxidation in vivo.

To address potential mechanisms for oxidative modification of lipids in vivo, we investigated the possibility that phospholipids react directly with glucose to form advanced glycosylation end products (AGEs) that then initiate lipid oxidation. Phospholipid-linked AGEs formed readily in vitro, mimicking the absorbance, fluorescence, and immunochemical properties of AGEs that result from advanced glycosylation of proteins. Oxidation of unsaturated fatty acid residues, as assessed by reactive aldehyde formation, occurred at a rate that paralleled the rate of lipid advanced glycosylation. Aminoguanidine, an agent that prevents protein advanced glycosylation, inhibited both lipid advanced glycosylation and oxidative modification. Incubation of low density lipoprotein (LDL) with glucose produced AGE moieties that were attached to both the lipid and the apoprotein components. Oxidized LDL formed concomitantly with AGE-modified LDL. Of significance, AGE ELISA analysis of LDL specimens isolated from diabetic individuals revealed increased levels of both apoprotein- and lipid-linked AGEs when compared to specimens obtained from normal, nondiabetic controls. Circulating levels of oxidized LDL were elevated in diabetic patients and correlated significantly with lipid AGE levels. These data support the concept that AGE oxidation plays an important and perhaps primary role in initiating lipid oxidation in vivo.

Adult↗

PubMed2001

An inner membrane enzyme in Salmonella and Escherichia coli that transfers 4-amino-4-deoxy-L-arabinose to lipid A: induction on polymyxin-resistant mutants and role of a novel lipid-linked donor.

Attachment of the cationic sugar 4-amino-4-deoxy-l-arabinose (l-Ara4N) to lipid A is required for the maintenance of polymyxin resistance in Escherichia coli and Salmonella typhimurium. The enzymes that synthesize l-Ara4N and transfer it to lipid A have not been identified. We now report an inner membrane enzyme, expressed in polymyxin-resistant mutants, that adds one or two l-Ara4N moieties to lipid A or its immediate precursors. No soluble factors are required. A gene located near minute 51 on the S. typhimurium and E. coli chromosomes (previously termed orf5, pmrK, or yfbI) encodes the l-Ara4N transferase. The enzyme, renamed ArnT, consists of 548 amino acid residues in S. typhimurium with 12 possible membrane-spanning regions. ArnT displays distant similarity to yeast protein mannosyltransferases. ArnT adds two l-Ara4N units to lipid A precursors containing a Kdo disaccharide. However, as shown by mass spectrometry and NMR spectroscopy, it transfers only a single l-Ara4N residue to the 1-phosphate moiety of lipid IV(A), a precursor lacking Kdo. Proteins with full-length sequence similarity to ArnT are present in genomes of other bacteria thought to synthesize l-Ara4N-modified lipid A, including Pseudomonas aeruginosa and Yersinia pestis. As shown in the following article (Trent, M. S., Ribeiro, A. A., Doerrler, W. T., Lin, S., Cotter, R. J., and Raetz, C. R. H. (2001) J. Biol. Chem. 276, 43132-43144), ArnT utilizes the novel lipid undecaprenyl phosphate-alpha-l-Ara4N as its sugar donor, suggesting that l-Ara4N transfer to lipid A occurs on the periplasmic side of the inner membrane.

Amino Sugars↗

PubMed2003

Lipid-dependent recruitment of neuronal Src to lipid rafts in the brain.

Although most Src family tyrosine kinases are modified by palmitoylation as well as myristoylation, Src itself is only myristoylated. Dual acylation is important for attachment to liquid-ordered microdomains or lipid rafts. Accordingly, Src is excluded from lipid rafts in fibroblasts. Evidence of partial genetic redundancy between Src and Fyn for brain-specific targets suggests that these two kinases may occupy overlapping subcellular locations. Neuronal Src (NSrc), an alternative isoform of Src with a 6-amino acid insert in the Src homology 3 domain, is highly expressed in neurons. We investigated whether this structural difference in NSrc allows it to associate with lipid rafts. We found that perinatal mouse brains express predominantly NSrc, which is partly (10-20%) in a lipid raft fraction from brain but not fibroblasts. The association of Src with brain lipid rafts does not depend on the NSrc insert but depends on the amino-terminal myristoylation signal. A crude lipid fraction from brain promotes NSrc entry into rafts in vitro. Moreover, lipid raft-localized NSrc is more catalytically active than NSrc from the soluble fraction, possibly because raft localization alters access to other tyrosine kinases and phosphatases. These findings suggest that NSrc may be involved in signaling from lipid rafts in mouse brain.

Animals↗

PubMedDate not supplied

Mitogenic activities of lipid A and liposome-associated lipid A: effects of epitope density.

Among eight purified lipid A fractions, there was heterogeneity of mitogenic activity, but the relative activity could not be predicted by limulus amebocyte lysate assay. Analysis of mitogenic activity after the incorporation of lipid A into liposomes demonstrated that epitope density of lipid A was a crucial factor that strongly modulated expression of lipid A. The results suggest that lipid A hydrophobic groups are responsible for mitogenic activity and that the surface accessibility of lipid A hydrophobic groups in membranes may be influenced by epitope density. The data are compared with previous results derived from parallel studies on limulus amebocytes. Both approaches lead to the conclusion that the activities of purified lipid A fractions are heterogeneous and that epitope density is critically important for the expression of biologic activity of membrane-associated lipid A.

Animals↗

PubMedDate not supplied

Defective responses to lipid A in C3H/HeJ mice: approaches to an understanding of lipid A-cell interaction.

C3H/HeJ mice have diminished responses to lipopolysaccharide (lipid A) that are due to a mutation in a gene located on chromosome 4. Studies employing this strain o mice have contributed significantly to our understanding of cellular interactions, mediators, and the genetic control involved in various host responses to lipid A. The present review emphasizes areas of research that require further elucidation, such as binding versus triggering sites for lipid A and the state of differentiation of the responding cells that is required for activation by lipid A. Certain experimental approaches to the investigation of the mechanisms of interaction of lipid A with target cells are suggested. Insertion of membrane fragments obtained from lipid A-sensitive cells into nonresponder cells has focused attention on the cell membrane as the primary target for lipid A. Thus, a clearer definition of either binding or triggering sites for lipid A could be gained by employing monoclonal antibodies to specific cell-surface components.

Animals↗

PubMed1987

Effects of dietary fiber, carbohydrate, lipid and protein levels on serum and liver lipids in rats.

Response-surface regression analysis was used to study dietary levels of fiber, carbohydrate, lipid and protein to minimize serum and liver cholesterol and triglyceride levels and maximize serum high-density lipoprotein-cholesterol levels of male weanling rats. Because the dietary components were not statistically independent, they were studied in combinations of three variables. The three-variable combinations were the most useful in locating the desired maximum or minimum lipid responses in terms of the proportions of the dietary components. These analyses indicated that dietary carbohydrate, lipid and protein were better than dietary fiber for predicting the serum and liver lipid response levels. Response-surface contours and three-dimensional plots were developed for each lipid response except serum triglycerides, which were not predictable. The contours and three-dimensional plots were used to help determine those combinations of the diet components that would produce the desired maximum or minimum lipid responses. The statistical analyses indicated that the desired lipid response levels could be attained with a diet consisting of 3-5% neutral detergent bran fiber, 6-10% lipid, 54-55% carbohydrate, 26-30% protein and 4.7% vitamins and minerals.

Animals↗

PubMed1986

Structure-activity relationship of lipid A: comparison of biological activities of natural and synthetic lipid A's with different fatty acid compositions.

To investigate the structure-activity relationships, various biological activities, including pyrogenicity, lethal toxicity, elicitation of Shwartzman reaction, mitogenicity and tumor necrosis factor (TNF)-inducing activity, were compared among natural and synthetic lipid A's differing in fatty acid composition. In all these tests, natural lipid A's from Escherichia coli and Salmonella minnesota and synthetic LA-15-PP, which carries 3-hydroxy- and 3-acyloxy-tetradecanoyl groups at the 2, 3 and 2', 3' positions, respectively, showed the strongest activities among the tested lipid A's. In contrast, LA-16-PP, in which the amide-bound 3-hydroxytetradecanoic acid at position 2 of LA-15-PP is replaced by 3-hexadecanoyloxytetradecanoic acid, exhibited lower activity than LA-15-PP and natural lipid A's. Although LA-16-PP has been assumed to have a typical Salmonella lipid A structure (and, in fact, it has a structure corresponding to one of the components of Salmonella lipid A), the activity of this synthetic compound was not comparable to that of natural Salmonella lipid A. LA-17-PP, in which tetradecanoic acid is the sole fatty acid component, exhibited relatively strong mitogenicity and TNF-inducing activity, but very low pyrogenicity. The activities of LA-18-PP, which has ester-bound tetradecanoic acid and amide-bound 3-hydroxytetradecanoic acid, were lower than those of LA-17-PP. The results indicate that the differences in fatty acid composition of lipid A's have important influences on the biological activities studied.

Animals↗

PubMed2006

Effect of lipid levels and lipid-lowering therapy on restenosis after coronary artery stenting.

BACKGROUND: Recent experimental and clinical data suggest that lowering serum lipid levels with statins may prevent or delay the process of restenosis. The purpose of this trial is to determine whether lipid levels relate to restenosis and/or whether statin therapy can prevent or delay the process of restenosis after intracoronary stenting. METHODS: One hundred thirty-six patients who underwent single coronary artery stenting from June 1995 to June 1997 in our institution were included in the study. All these patients were followed for at least 9 months (mean 392+/-148 days) for major adverse cardiac events (MACE). We defined as MACE the occurrence of death, myocardial infarction, or need for target lesion revascularization. From this cohort, 103 patients had at least one lipid parameter from the lipid profile evaluated within 2 months from the date of the procedure. Patients who had the stent because of an acute myocardial infarction were included in the study only if their lipid profile was evaluated before or at least 6 weeks after the event. Patients with triglyceride levels above 500 had both triglyceride and low-density lipoprotein cholesterol levels excluded from the statistical analysis. Patients were divided into two groups based on lipid levels: normal (Group I; n=31) and elevated (Group II; n=72). Patient outcomes were also analyzed by statin therapy use. RESULTS: There was no significant difference in MACE rates between the two groups when outcomes were analyzed by lipid levels (22.6% versus 20.8% P=0.8). Furthermore, outcomes were analyzed by use of statin therapy (Group III, n=53, on statin versus Group IV, n=50, on no statin). There was also no difference in MACE rates between the two groups (20.8% versus 22%; P=0.8). CONCLUSION: The process of restenosis has unique features that differentiate it from atherosclerosis. Although lipid-lowering therapy is crucial in delaying the process of atherosclerosis, its role in the prevention of restenosis is yet to be proven.

Aged↗

PubMed2007

Comparison of the efficacy of two lipid emulsion eyedrops in increasing tear film lipid layer thickness.

PURPOSE: The lipid layer of the tear film is critical to maintaining the thickness of the multilayered tear film. This study was designed to determine whether a single drop of Refresh Dry Eye Therapy or Soothe, both lipid emulsion eyedrops, significantly increased the lipid layer thickness (LLT) of patients with self-reported dry eyes and thin lipid layers. METHODS: Lipid layer interference patterns were used to quantify the LLT of both eyes of eligible patients before and after test drop instillation. Patients (n=41) reporting dry eye symptoms and having baseline LLT of no more than 75 nm received 40 microL of Refresh Dry Eye Therapy in one eye and 40 microL of Soothe in the contralateral eye. After instillation, LLT was quantified at 1, 5, and 15 minutes. LLT after drop instillation was averaged for the three time points. RESULTS: The mean +/- standard error baseline LLT was 59.6 +/- 1.7 nm for eyes treated with Refresh Dry Eye Therapy and 61.5 +/- 1.6 nm for eyes treated with Soothe. These means were not significantly different (P>0.05). The overall mean LLT after drop instillation was 83.2 +/- 3.6 nm for Refresh Dry Eye Therapy (P<0.0001) and 121.5 +/- 3.8 nm for Soothe (P<0.0001). The mean LLT increase from Soothe (60.0 nm) was significantly greater than that from Refresh Dry Eye Therapy (23.6 nm) (P<0.0001). CONCLUSIONS: The application of a lipid emulsion eyedrop will increase LLT and benefit patients with deficient lipid layers who experience dry eye symptoms. Although both products are lipid emulsions, one drop of Soothe essentially doubled LLT and provided a mean increase in LLT that was 2.5 times greater than that of Refresh Dry Eye Therapy.

Adolescent↗

PubMed1998

Phenotypic variation of lipid composition in Burkholderia cepacia: a response to increased growth temperature is a greater content of 2-hydroxy acids in phosphatidylethanolamine and ornithine amide lipid.

Burkholderia cepacia produces an unusual range of polar lipids, which includes two forms each of phosphatidylethanolamine (PE) and ornithine amide lipid (OL), differing in the presence or absence of 2-hydroxy fatty acids. By using chemostat cultures in chemically defined media, variations in the lipid content and the proportions of individual lipids have been studied as a function of (a) growth temperature, (b) growth rate and (c) growth-limiting nutrient (carbon, magnesium, phosphorus or oxygen). Total cellular lipid in carbon-limited cultures was lowest at high growth temperatures and low growth rates. Increases in growth temperature over the range 25-40 degrees C led to increases in the proportions of molecular species of PE and OL containing 2-hydroxy acids, without changing the PE:OL ratio. Growth temperature did not alter the balance between neutral and acidic lipids, but the contribution of phosphatidylglycerol to the latter increased with rising growth temperature and growth rate. Pigmentation of cells and the presence of flagella were also temperature-dependent. Change in growth rate also affected the PE:OL ratio and the extent to which monoenoic acids were replaced by their cyclopropane derivatives. Whereas similar lipid profiles were found for carbon-, magnesium- and oxygen-limited cultures, ornithine amides were the only polar lipids detected in phosphorus-limited cells.

Burkholderia cepacia↗

PubMed1978

Membrane lipid metabolism in Acholeplasma laidlawii A EF 22. Influence of cholesterol and temperature shift-down on incorporation of fatty acids and synthesis of membrane lipid species.

1. Membrane lipid metabolism in Acholeplasma laidlowii A EF 22 has been studied under different conditions by applying three different techniques for changing membrane viscosity: fatty acid and cholesterol supplementation and temperature changes. 2. The molar relationship between the two dominating membrane lipids, monoglucosyldiglyceride and diglucosyldiglyceride, is to a large extent determined by membrane viscosity properties. This is shown by the varying metabolic responses occurring during incorporation of different fatty acids with and without cholesterol and by temperature shift-down experiments. Higher viscosity in membranes stimulates synthesis of monoglucosyldiglyceride at the expense of diglucosyldiglyceride. Synthesis of phospho and phosphoglucolipids is affected as well. 3. Temperature shift-down from 37 degrees C to 17 degrees C results in an immediate synthesis of monoglucosyldiglyceride accompanied by an increased incorporation of unsaturated fatty acids into this lipid. Synthesis of the other membrane lipid species (containing more unsaturated fatty acids) lags behind temporarily. 4. Incorporation from an equimolar mixture of palmitic and oleic acids together with cholesterol yields greater amounts of oleic acid in membrane lipids than incorporation in the absence of cholesterol, indicating that incorporation is viscosity dependent. 5. Studies of precursor relationships reveal that all main lipids have an active turnover which differs depending on membrane composition and conditions. Furthermore, this turnover proceeds with different intra-lipid pools. 6. Isolated membranes contain no detectable lipolytic enzymes capable of hydrolyzing membrane phospho or glycolipids. It is suggested that lipid turnover is partly mediated by enzymatic interlipid conversions, thus not allowing intermediates to accumulate.

Acholeplasma laidlawii↗

PubMed2006

Porphyromonas gingivalis lipopolysaccharide lipid A heterogeneity: differential activities of tetra- and penta-acylated lipid A structures on E-selectin expression and TLR4 recognition.

Porphyromonas gingivalis is a gram-negative bacterium strongly associated with periodontitis, a chronic inflammatory disease of the tissue surrounding the tooth root surface. Lipopolysaccharide (LPS) obtained from P. gingivalis is unusual in that it has been shown to display an unusual amount of lipid A heterogeneity containing both tetra- and penta-acylated lipid A structures. In this report, it is shown that penta-acylated lipid A structures facilitate E-selectin expression whereas tetra-acylated lipid A structures do not. Furthermore, it is shown that tetra-acylated lipid A structures are potent antagonists for E-selectin expression. Both tetra- and penta-acylated lipid A structures interact with TLR4 although experiments utilizing human, mouse and human/mouse chimeric TLR4 proteins demonstrated that they interact differentially with the TLR4 signalling complexes. The presence of two different structural types of lipid A in P. gingivalis LPS, with opposing effects on the E-selectin response suggests that this organism is able to modulate innate host responses by alterations in the relative amount of these lipid A structures.

Animals↗

PubMed1994

Effects of glucose-to-lipid ratio and type of lipid on substrate oxidation rate in patients.

This study is an investigation into the effects of different carbohydrate-to-lipid ratios on CO2 production in postoperative patients and the determination of the substrate oxidation rates induced by long-chain triglycerides (LCT) or a mixture of long- and medium-chain triglycerides (MCT/LCT) at various carbohydrate-to-lipid ratios. Two groups of eight patients randomly received either LCT or MCT/LCT emulsions. Total caloric intake was set at the measured energy expenditure provided at three different glucose-to-lipid ratios (70:30, 50:50, 30:70). We used long-term indirect calorimetry with a mass spectrometer system and measurement of natural enrichment in 13C of expired CO2 and plasma glucose. The carbon dioxide production and minute ventilation were not different among the different glucose-to-lipid ratios, whatever the type of lipid. Increasing the lipid supply up to 70% of nonprotein caloric intake led to an only minor increase in lipid oxidation rate and thus to a net fat deposit. We conclude that large amounts of lipid (LCT or MCT/LCT) were not of interest in such patients.

Aged↗

PubMed1970

Evidence for the chylomicron origin of lipids accumulating in diabetic eruptive xanthomas: a correlative lipid biochemical, histochemical, and electron microscopic study.

Plasma lipoprotein alterations in nine insulin-dependent diabetics with hyperlipemia have been related to the lipid accumulating in eruptive xanthomas evolving in these patients. Histochemical and electron microscopic examination of xanthomas have been correlated with the lipid analyses in order to obtain additional evidence regarding the lipoprotein origin of lipids accumulating in the lesions. Both analytical and morphologic evidence suggested that circulating chylomicrons significantly contribute to the xanthoma lipids. All the patients had large quantities of circulating triglyceriderich chylomicrons which carried approximately 70% of the triglyceride found in the plasma. The fatty acid pattern of chylomicron and xanthoma triglycerides were similar. Triglyceride constituted the major lipid found in the xanthomas when they were sampled during their eruption. These findings, take in conjunction with histochemical and electron microscopic evidence of chylomicron particles in the dermal capillary walls, support the theory that blood lipoproteins, and particularly chylomicrons, permeated the vascular walls and the triglycerides carried by these lipoproteins apparently accumulated in tissue macrophages and perithelial cells which evolved into foam cells. Initiation of appropriate therapy resulted in clearance of the chylomicronemia and a concomitant resolution of the xanthomas as reflected by a decrease in total xanthoma lipid. Sequential studies of resolving xanthomas in five patients revealed that xanthoma triglyceride was mobilized more rapidly than cholesterol, resulting in a redistribution of the xanthoma lipids, so that the resolving lesions were cholesterol rich. Consistent with this change in lipid composition, correlative electron microscopy revealed loss of amorphous material from many of the foam cell vacuoles.

Capillaries↗