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Hypertriglyceridaemia has been associated with cardiovascular disease risk in humans for several decades. However, only recently, data from basic research, as well as from genetic and observational studies, have suggested triglyceride-rich lipoproteins (TRLs) as causal factors for atherosclerotic cardiovascular disease. Novel findings highlighting the relevance of TRL-derived lipolytic products (remnant lipoprotein particles "RLPs"), rather than plasma triglycerides or TRL themselves, as the true mediators in atherosclerosis, have contributed to explain a causal relationship through a number of direct and indirect mechanisms. Thus, experimental studies in animal models and in vitro cell culture methods reveal that RLPs, having sizes below 70-80nm, enter the arterial wall and accumulate within the sub-endothelial space. They then become involved in the cholesterol deposition of cholesterol in the intima in addition to several pro-inflammatory and pro-apoptotic pathways. In this review, a summary is presented of current understanding of the pathophysiological mechanisms by which TRLs and their lipolytic derived RLP induce the formation and progression of atherosclerotic lesions, and actively contribute to cardiovascular disease.

The cholesterol in bile is absorbed by the gallbladder epithelium and taken up by macrophages and accumulates in the lamina propria. Cholesterol deposition within the lamina propria creates a mass and protrudes out of the mucosa into the lumen, and these masses are called cholesterol polyps.

Cholesterol metabolism becomes imbalanced during the formation of macrophage-derived foam cells. Pre-B-cell colony-enhancing factor (PBEF) has recently been found to affect lipid deposition and inflammation in atherosclerosis. Here, we aimed to study the effects and molecular mechanism of Polydatin on atherosclerosis in ApoE-knockout (ApoE[Formula: see text]) mice. Thirty ApoE[Formula: see text] mice were fed a high-fat diet (HFD) for 12 weeks, and then treated with Polydatin for another 12 weeks. Whole aortas and cryosections were stained with oil red O. Blood lipid, PBEF and cytokine levels were measured by ELISA. The mRNAs of cholesterol metabolism-related genes were determined by qRT-PCR and protein levels by Western blotting. Cell cholesterol content and viability were determined in macrophages and RAW 264.7 cells. PBEF siRNA was used to study the effect of Polydatin on cholesterol metabolism in macrophages incubated with ox-LDL. Polydatin lowered blood lipids and decreased atherosclerotic lesions in ApoE[Formula: see text] mice. The expression of cytokines and the mRNA of cholesterol metabolism-related genes were markedly regulated by Polydatin. Meanwhile, PBEF mRNA and protein were both greatly down-regulated by Polydatin. In vitro, Polydatin protected RAW 264.7 cells treated by ox-LDL and inhibited cholesterol uptake by macrophages. The PBEF siRNA result indicates that Polydatin can modulate cholesterol metabolism in macrophages, partly through down-regulation of PBEF. In conclusion, Polydatin relieves atherosclerosis injury in ApoE[Formula: see text] mice, mainly through down-regulation of PBEF and inhibition of PBEF-inducing cholesterol deposits in macrophages.

The aim of the present study was to determine the effects of feeding of a high-fat diet containing different types of lipids for four weeks on the cholesterol and triglyceride contents of different fat depots and on body temperature in rats. Four groups of adult rats were fed 10% fat, containing either beef tallow, safflower oil, or fish oil, respectively, as well as a normal rodent diet with 4% fat, for four weeks. The rats on normal rodent diet consumed significantly more food and water than the rats in the other three groups. Rectal temperature increased only after four-week feeding with safflower oil fat. Increased fat deposition and adipocyte size were observed in rats fed safflower oil and beef tallow. In all fat pads of safflower oil-fed rats, cholesterol content was significantly higher than the other three groups. Feeding of beef tallow increased triglyceride depot without increasing cholesterol content. The rats fed fish oil had significantly less triglyceride and cholesterol deposition in adipose tissues than the rats fed safflower oil or beef tallow. These results clearly demonstrated the differences in fat deposition, adipocyte size and number, triglyceride and cholesterol accumulation in fat cells are dependent on the dietary lipid composition.

The fermentation concentrate of Hericium caput-medusae (Bull.:Fr.) Pers. (HFC) is a liquid fermentation product of fungi. The purpose of this study was to investigate the effects of dietary supplementation with HFC on cholesterol deposition in the liver and meat, as well as the production of short chain fatty acids (SCFA) in the cecum of broiler chickens. A total of 480 male broiler chickens (1- d -old, initial body weight of 38.8 ± 0.9 g) were randomly assigned to 4 dietary treatments with 6 cages/treatment and 20 broiler chickens/cage. The broiler chickens in the 4 treatments received diets supplemented with 0, 0.6, 1.2, and 1.8% of HFC during the 42-d feeding experiment. The results showed that the serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol concentrations decreased linearly (P

Once thought to be solely a matter of cholesterol deposition in arterial walls, atherosclerosis and, in particular, thrombosis of an atherosclerotic lesion is now known to be dependent on activation and deposition of platelets aided by the coagulation system. Although aspirin had been used as an anti-inflammatory and antipyretic agent since 1900, it wasn’t until 1970 that aspirin was discovered to have powerful and durable antiplatelet activity. Over the past several decades, an enormous amount of research has revealed both the role of platelets in atherogenesis and, in particular, acute thrombosis of the atherosclerotic plaque. This chapter reviews the physiology, pathology, and pharmacology of this event. Modern therapy as it relates to primary and secondary prevention as well as intervention addressing atherosclerotic myocardial ischemia is addressed.

Fifty-four crossbred, castrated male pigs with an average initial weight of 10.2 kg were fed diets containing either 1 or 3 times the daily requirement of calcium and 1, 5 or 25 times the daily requirement of cholecalciferol in a 2 X 3 factorial design. During week 6, pigs were fitted with femoral artery, coimnon bile duct and re-entrant duodenal catheters. Eighteen pigs died during or after surgery, giving a mortality rate of 33%. Causes of death included intestinal blockage, euthanasia after catheter failure, gastric ulcer, infection and death during surgery. Body weight of pigs at weeks 7 and 8 were greater (P

Chronic inflammatory demyelinating polyradiculoneuropathy occurred in an 11-year-old Labrador Retriever dog. Spinal cord compression resulted from massive radiculitis with prominent cholesterol granulomas. Cholesterol deposition and associated granuloma formation is unique in chronic inflammatory demyelinating polyradiculoneuropathy, in both its human and canine expressions.

Atherosclerosis is characterized by the accumulation of lipids within the arterial wall and is commonly diagnosed using standard histology. Non-linear microscopy represents a possible label-free alternative to standard diagnostic methods for imaging various tissue components. Here we employ SHG and CARS microscopy for imaging thin cross-sections of atherosclerotic arterial tissue, demonstrating that both cholesterol deposition in the lumen and collagen in the normal arterial wall can be imaged and discriminated using SHG and CARS microscopy. A simultaneous detection of both forward and backward scattered SHG signals allows distinguishing collagen fibres from cholesterol. Further analysis, based on image pattern evaluation algorithms, is used to characterize collagen organization in the healthy arterial wall against collagen found within plaques. Different values of fibre mean size, distribution and anisotropy are calculated for lumen and media prospectively allowing for automated classification of atherosclerotic lesions. The presented method represents a promising diagnostic tool for evaluating atherosclerotic tissue.

Familial hypercholesterolemia is characterized by a major elevation in circulating LDL-cholesterol levels, cholesterol deposition within the arterial wall and an increased risk of premature coronary artery disease. The reverse cholesterol transport (RCT) is now considered as a key process that protects against development of atherosclerosis. The major antiatherogenic action of HDL particles is intimately linked to their determinant role in RCT pathway. However, the steady-sate of HDL-cholesterol levels does not represent the optimal marker to evaluate the efficiency of the RCT in all circumstances.By using ex-vivo systems for the evaluation of the efficacy of RCT a strong inverse relationship between HDL efflux capacity from macrophages and atherosclerosis progression has been demonstrated. Low HDL-C phenotype observed in familial hypercholesterolemia patients is associated with defective capacities of HDL particles to mediate major steps of the centripetal movement of cholesterol from peripheral cells to feces. However, current available treatment used to reduce LDL-C to therapeutic goals does not correct altered functions of HDL particles in humans.In the context of familial hypercholesterolemia, a growing body of evidence suggests that impaired efficacy of the RCT pathway contributes significantly to the progression of atherosclerosis.

Numerous epidemiologic and interventional studies revealed that high-density lipoprotein (HDL) is an important risk factor for coronary heart disease. There are several well documented HDL functions that may account for the antiatherogenic effects of this lipoprotein. The best recognized of these is the capacity of HDL to transport cholesterol from the periphery to the liver, and thereby prevent cholesterol deposition in the arterial wall. Further properties of HDL that may also be antiatherogenic include its potent anti oxidative and anti-inflammatory action. In addition, HDL seems to be involved in processes related to senescence at both the cellular and whole-organism level. Both protein components of HDL (such as apolipoprotein A-I) and its lipid components (such as, lysosphingolipids) appear to mediate the antiatherogenic and anti-aging effects of HDL. The purpose of this review is to summarize the novel functions of HDL that may protect from atherosclerosis and senescence.

SUMMARY 1. Atherosclerosis begins with the deposition of cholesterol in arterial tissue that is thought to be derived from circulating lipoproteins. There is considerable evidence implicating low density lipoprotein (LDL) as a primary source of plaque cholesterol and, consequently, there are many articles that deal with various aspects of LDL metabolism. 2. Postprandial lipoproteins (i.e. chylomicrons transporting dietary fats) are also considered pro-atherogenic; however, it is less clear whether their involvement in arterial cholesterol deposition is direct or follows modulation of LDL metabolism. 3. In order to provoke discussion, this article is presented in a manner that suggests atherosclerosis to be exclusively a postprandial phenomenon; that is, we have raised the possibility that LDL is non-atherogenic.

Residual cardiovascular risk is often associated with lipid abnormalities, such as atherogenic dyslipidaemia (AD). Dyslipidaemias are one of the determinants of the risk of developing atherosclerotic cardiovascular disease. In addition to low-density lipoprotein (LDL) particles, which are the most atherogenic lipoproteins, other apolipoprotein B-containing lipoproteins [e.g. triglyceride (TG)-rich lipoproteins and their remnants] contribute to intimal cholesterol deposition and to the development of atherosclerosis. Lipoprotein size is a key determinant of atherogenesis, with remnants being able to penetrate the arterial intima and bind to and be retained by connective matrix tissue, thus directly contributing to plaque formation and progression. This is particularly …

Apolipoprotein (apo) E-deficient mice were fed a hypercholesterolemic diet for 14 weeks. Mean serum cholesterol levels rose to 37.5 mM. Upon complete necroscopy, massive xanthomatous lesions were noticed in various tissues, with a predilection for subcutaneous and peritendinous tissues, while control animals on the same diet (3.4 mM serum cholesterol) and apo E-deficient mice on a regular chow diet (20 mM serum cholesterol) did not show such lesions. Also, apo E3-Leiden transgenic mice fed a high fat diet, with 60 mM of serum cholesterol, did not exhibit any xanthomatosis. The xanthomatous lesions found in the Apoe knock-out mouse clearly differed in location from xanthomas previously found in low density lipoprotein receptor-deficient mice. We conclude that the lack of apo E results in atypical disseminated xanthomatosis, suggesting that apo E has an important role in determining the tissue distribution of cholesterol deposition. Chemicals/CAS: cholesterol, 57-88-5; Apolipoproteins E; Cholesterol, Dietary

Purpose. To analyze the impact of intermittent air exposure on the in vitro deposition of two radioactive lipids on variouscontact lens (CL) materials, using a custom-designed model blink cell.Methods. Six different CL materials (balafilcon A, lotrafilcon B, comfilcon A, senofilcon A, etafilcon A, and omafilcon A)were mounted on the model blink cell pistons, which cycled the lenses in and out ofa complex artificial tear solution (ATS)that contained a trace amount of 14 C-cholesterol or 14 C-phosphatidylcholine. For the short-term experiment, air-exposedlenses were continuously cycled in and out of the ATS for 10 h. Longer term incubations for 6 days were tested withlotrafilcon B and balafilcon A materials incubated in 14 C-cholesterol ATS. The air-exposed CLs were cycled for 14 h thensubmerged for 10 h each day. For both experiments, the control lenses were submerged for the entire test period. Afterincubation, lenses were processed, and deposited masses were quantified.Results. Exposure to air resulted in increased amounts of cholesterol deposited by 1.6 to 4.3 fold on omafilcon A, bala-filcon A, comfilcon A, and senofilcon A (p e0.03) compared with submerged lenses. No differences in deposition wereobserved for etafilcon A and lotrafilcon B (p 90.05). The longer term incubation of lotrafilcon B and balafilcon A showedstatistically significant increases in cholesterol deposition for both air-exposed lens materials (p G0.02) with the increase indeposition 1.8 and 2.8 , respectively. For phosphatidylcholine, all air-exposed lenses had increased masses of depo-sition. These deposits were statistically greater by 1.1 to 1.6 times for omafilcon A, comfilcon A, lotrafilcon B, andsenofilcon A (p G0.04), but not statistically different for etafilcon A or balafilcon A (p 90.05).Conclusions. This study found that lipid deposition profiles are CL material dependent and that intermittent air exposurecan influence the mass of lipid deposited.(Optom Vis Sci 2012;89:1574Y1581)Key Words: lipid, deposition, contact lens, tear film

Functional properties of fats and oils do not depend only on their fatty acid composition but also on the distribution of these fatty acids in the three positions of the glycerol backbone. This gives the fat or oil its commercial value. (Zhao,2005) There is a growing demand for lipids with desired characteristics ,thus researches have given way to these demands by the development of structured lipids with triacylglycerols that have predetermined composition and distribution of fatty acids. Structured lipids are now considered as alternatives to conventional fats not on the basis of saturate/polyunsaturate ratios but rather on their impact on cholesterol deposition. With the advances in the biotechnology and chemistry of fats and oils it is now possible to design fats and oils with properties that are desired. Recent years have seen great interest in the biotechnological modification and synthesis of structured triacylglycerols. Modification of fats and oil triacylglycerols to improve functionality have been carried out with various oils including olive oil. Olive oil enjoys a privileged position amongst edible oils and is still a buoyant commerce because of the large consumption of Mediterranean inhabitants (Oh et al,2009). It is one of the most expensive vegetable oils and of all the vegetable oils, olive oil is the best source of the monounsaturated fatty acid, oleic acid (72-83%)Risk factors for cardiovascular disease such as the level of homocysteine and total and low density lipoprotein (LDL) cholesterol in plasma have been reported to be reduced by oleic acid (Baro et al,2003). Olive oil is more than just oleic acid and because of its properties and qualities, it is used almost entirely in dietary consumption and even new markets have been created for this oil.

The build-up of cholesterol in the walls of arteries is a hallmark of atherosclerosis. Work with transgenic mice has revealed a specific interaction through which cholesterol deposition is initiated.

Purpose To examine the effect of cholesterol on the adhesion of bacteria to silicone hydrogel contact lenses. Methods Contact lenses, collected from subjects wearing Acuvue Oasys or PureVision lenses, were extracted in chloroform:methanol (1:1, v/v) and amount of cholesterol was estimated by thin-layer chromatography. Unworn lenses were soaked in cholesterol, and the numbers of Pseudomonas aeruginosa strains or Staphylococcus aureus strains that adhered to the lenses were measured. Cholesterol was tested for effects on bacterial growth by incubating bacteria in medium containing cholesterol. Results From ex vivo PureVision lenses, 3.4 ± 0.3 μg/lens cholesterol was recovered, and from Acuvue Oasys lenses, 2.4 ± 0.2 to 1.0 ± 0.1 μg/lens cholesterol was extracted. Cholesterol did not alter the total or viable adhesion of any strain of P. aeruginosa or S. aureus (p > 0.05). However, worn PureVision lenses reduced the numbers of viable cells of P. aeruginosa (5.8 ± 0.4 log units) compared with unworn lenses (6.4 ± 0.2 log units, p = 0.001). Similarly, there were fewer numbers of S. aureus 031 adherent to worn PureVision (3.05 ± 0.8 log units) compared with unworn PureVision (4.6 ± 0.3 log units, p = 0.0001). Worn Acuvue Oasys lenses did not affect bacterial adhesion. Cholesterol showed no effect on the growth of any test strain. Conclusions Although cholesterol has been shown to adsorb to contact lenses during wear, this lipid does not appear to modulate bacterial adhesion to a lens surface.

International audience; Aim: Dietary supplements in polyunsaturated fatty acids (PUFA), particularly omega-3, are well known for their beneficial effects in preventing cardiovascular diseases (CVD). The aim of this study was to determine the role of PUFA on the modulation of apoptosis induced by hypochlorous acid-oxidized LDL (HOCl-oxLDL) in U937 cells. Methods: We tested the effect of monocyte cell line U937 supplementation with eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (ARA) or oleic acid (OA) on the modulation of HOCl-oxLDL-induced apoptosis. Results: First, we showed the incorporation of fatty acids in the cellular membrane in U937 cells. Then, we showed that both EPA and ARA exerted a pro-apoptotic effect through the intrinsic mitochondrial apoptotic pathway including the dissipation of mitochondrial membrane potential followed by cardiolipin depletion, the downstream activation of caspase-3 and the increase in DNA fragmentation. The pro-apoptotic effect of EPA or ARA was completely blocked in U937/Bcl-2 cells. Conclusions: A new mechanism of dietary supplements in PUFA with likely consequences in apoptosis could be suggested through the mitochondrial pathway in monocytes.

Background: Schnyder's crystalline dystrophy is a central anterior bilateral corneal dystrophy characterized by the deposition of crystals composed of cholesterol and other lipids. This condition classically is described as nonprogressive after childhood, but a series of recent studies following patients over time has challenged this teaching. Patients: The authors present a family pedigree including a patient first reported in 1954 and followed for 25 years with dramatic progression of the corneal condition in a dense, discoid pattern of crystals. Best-corrected visual acuity decreased from 20/ 30 to 20/80 in both eyes. This patient now has three children, all with typical corneal involvement. Results: Ocular pathologic examination performed on corneal biopsies submitted for light and electron microscopy demonstrated cholesterol deposition consistent with a diagnosis of Schnyder's. Conclusion: Schnyder's corneal dystrophy may progress significantly over time. The characterization of this condition as stationary may need to be reconsidered.

Schnyder's crystalline dystrophy is an uncommon hereditary disease in which there is abnormal deposition of cholesterol and/or lipid usually in the anterior stroma of the central and peripheral cornea. Four families with Schnyder's dystrophy have been identified in central Massachusetts. Of the 173 living members of these pedigrees, 60 patients were examined by the author. Eighteen patients had Schnyder's dystrophy. Affected individuals less than 23 years of age had bilateral, central disc-like corneal opacification. Those greater than 23 years of age also demonstrated prominent arcus lipoides. By age 40, all affected individuals developed a diffuse stromal haze. Only 50% of affected individuals had corneal crystalline deposits. Abnormal cholesterol deposition affected the entire stromal thickness in the majority of patients. Although the four families said that they were not related to each other, all had ancestry from towns within a 100-k area on the southwest coast of Finland. Patients in this area of Finland were examined by the author and demonstrated signs of Schnyder's dystrophy. This may represent the largest cohort of Schynder's dystrophy described to date.

Amyloid plaques and neurofibrillary tangles are prominent lesions in the aging brain and they may be responsible for cell death in Alzheimer's disease. But a basic question has not been answered: why and how are plaques and tangles formed during aging? In this study, we approach this question by first examining what happens in the aging body. Plaques and tangles do not come alone, but together with many other aging markers in the body (cholesterol deposition, gallstones, hair graying, and bone loss, etc.). Because these aging markers occur to a certain extent in all elderly and at about the same time in life, it is reasonable to conceive that they originate from a common cause, that is, aging-induced metabolic inefficiency. If cholesterol and gallstone depositions are the results of inefficient degradation/clearance of lipids and minerals, then similarly plaque and tangle formation in most people would be the results of inefficient normal degradation of ?-amyloid precursor protein (APP) and tau, respectively. By this view, our studies should focus on the enzymes responsible for APP and tau normal degradation and their natural changes in aging, rather than on presumed pathological factors. Whatever precise mechanisms underlying their depositions, plaques and tangles are the natural products of aging, thus fundamentally different from pathological events such as cancer growth in concept.

Hypercholesterolemia has been identified as a risk factor for bioprosthetic valvular degeneration, and it has been suggested that statin therapy reduces this risk. The case of a 77-year-old man with low levels of low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B who developed marked LDL-C crystal deposition and a severe foreign body giant cell reaction 21.5 years after aortic bioprosthetic replacement is reported. This observation confirms that cholesterol deposition contributes to bioprosthetic valve degeneration, but that this can occur even in patients with low levels of LDL-C. It suggests that the characteristics of the valve are more critical than the patient’s level of LDL-C.

Cholesterol is a molecule of great biomedical significance. We cannot live without it, and often, we cannot live with it. Cholesterol accumulation in blood vessels leads to the development of atherosclerotic plaque-like lesions. Heart attacks and some types of strokes occur when these plaques rupture and blood clots form on their surfaces. In the United States, heart attacks and strokes kill more than 500,000 people each year (American Heart Association, 1995).

Apolipoprotein (apo) E-deficient mice were fed a hypercholesterolemic diet for 14 weeks. Mean serum cholesterol levels rose to 37.5 mM. Upon complete necroscopy, massive xanthomatous lesions were noticed in various tissues, with a predilection for subcutaneous and peritendinous tissues, while control animals on the same diet (3.4 mM serum cholesterol) and apo E-deficient mice on a regular chow diet (20 mM serum cholesterol) did not show such lesions. Also, apo E3-Leiden transgenic mice fed a high fat diet, with 60 mM of serum cholesterol, did not exhibit any xanthomatosis. The xanthomatous lesions found in the Apoe knock-out mouse clearly differed in location from xanthomas previously found in low density lipoprotein receptor-deficient mice. We conclude that the lack of apo E results in atypical disseminated xanthomatosis, suggesting that apo E has an important role in determining the tissue distribution of cholesterol deposition. Chemicals/CAS: cholesterol, 57-88-5; Apolipoproteins E; Cholesterol, Dietary

1. We compared the serum and aortic lipid levels in spontaneously hypertensive rats (SHR) and Dahl salt-sensitive rats (DSR) fed a high-cholesterol (HC) diet. 2. In SHR fed the HC diet, the serum cholesterol level significantly increased, but no aortic cholesterol deposition was observed. 3. The serum cholesterol level in DSR fed the HC diet markedly increased compared to that in DSR fed the basal diet, and this change was greater with the diet containing 8% NaCl than 0.4% NaCl. A significant increase in the content of aortic cholesterol, notably cholesteryl ester, was observed in only DSR fed the HC diet containing 8% NaCl. 4. These results suggest that the combination of hypercholesterolaemia with salt-induced hypertension acts as a greater risk factor for atherosclerosis than that with genetic hypertension.

Rats were fed varying levels of flaxseed for three weeks. The diets were designed to provide 10%. 15%, and 20% flaxseed oil, respectively. The diets also contained 0.5% cholesterol and 0.2% cholic acid. Liver weight increased with increasing levels of fat. Serum cholesterol levels rose with increasing levels of fat, but HDL cholesterol and triglycerides were unaffected. Considering the presence of both cholesterol and cholic acid in the diet, the elevations of serum cholesterol were modest, which may reflect a potent hypocholesterolemic effect of linolenic acid. Liver total cholesterol levels fell with increasing levels of dietary flaxseed. Liver cholesterol ester levels (%) were lower in rats fed higher doses of flaxseed, indicating reduced cholesterol deposition. Liver triglyceride levels were the same in all three dietary groups. Calculations of the serum plus liver cholesterol pool showed them to be 334 mg, 273 mg, and 252 mg for rats fed 10%, 15%, or 20% flaxseed oil, respectively. Since high levels of flaxseed reduced cholesterol deposition in liver, it might be useful to test in experimental atherosclerosis.

• A 63-year-old woman with fibrous histiocytomas showed cholesterol deposition in the setting of type IIB hyperlipidemia. The two lesions involved the left leg and right thigh. One had typical features of a fibrous histiocytoma including changes of the overlying epidermis. The other was essentially replaced by cholesterol deposits and could not be differentiated from a tuberous xanthoma. This case illustrates the histiocytic response of fibrous histiocytomas to a hyperlipoproteinemic microenvironment. ( Arch Dermatol. 1990;126:506-508)

In summary, the study of type III hyperlipoproteinemia has provided important insights into lipoprotein metabolism that have helped to elucidate several functional roles for apo E and have provided a better understanding of the mechanisms whereby specific lipoproteins may be atherogenic or anti-atherogenic. The molecular defect in type III hyperlipoproteinemia and dysbetalipoproteinemia is the presence of a mutant form of apo E, usually apo E2, that is defective in binding to both apo B,E(LDL) and apo E receptors. The receptor-defective apo E results in an impaired clearance of remnant lipoproteins (beta-VLDL). In addition, the abnormal apo E may impair the lipolytic processing of hepatic beta-VLDL through its involvement in lipid transfer or exchange processes. The accumulation of beta-VLDL may provide the most direct mechanism responsible for the accelerated atherosclerosis observed in type III hyperlipoproteinemia, a mechanism that involves the receptor mediated uptake of beta-VLDL by macrophages, which are then converted to arterial foam cells. Alterations in the HDL of patients with type III hyperlipoproteinemia further support the concept that HDL are anti-atherogenic. The increase in HDL-with apo E provides insight into the role of these cholesterol-enriched HDL in reverse cholesterol transport and in the cellular redistribution of cholesterol, processes whereby cholesterol deposition may be reversed. It should be stressed that both the accumulation of beta-VLDL and alterations in HDL (reduction in typical HDL and an increase in HDL-with apo E) are associated with accelerated atherogenesis in animals fed high levels of fat and cholesterol. Although valuable information has been gained concerning the mechanisms involved in type III hyperlipoproteinemia by the study of the disease, the clinical expression of this disorder is variable, ranging from hypocholesterolemia to marked hypercholesterolemia in subjects with the same molecular defect (E2/2). This variability in expression is more easily understood when one considers the various factors that can promote the hyperlipoproteinemia and when one considers the mechanisms of action whereby these factors may exacerbate the effects of the presence of an abnormal apo E. In most cases, development of type III hyperlipoproteinemia requires that a second event (a predisposing environmental factor or a second genetic defect) be associated with the primary genetic defect (an abnormal form of apo E).

Four hundred and eighty, sexed (White Leghorn) chicks were divided so that each sex was fed one of eight rations to determine the effect of sex, dietary cholesterol, and stearic, oleic, and/or linoleic acid on cholesterol deposition in blood, liver and aortic tissues. After 5 months on the dietary regimen, 3 cockerels from each of the rations were orally administered 100 mC. sodium-1-C14-acetate and 200 mC. cholesterol-1,2-H3 to determine whether body tissues contained cholesterol from endogenous or exogenous origin. After 5 months on the experimental rations it was observed that male birds had higher free cholesterol levels than did females. The addition of cholesterol (2%) and fatty acids (6%) to ration increased free cholesterol levels in liver and aorta. Cholesterol stored in livers and aortas occurs principally as free cholesterol while blood cholesterol was in esterified form. Cholesterol levels in both liver and aorta are primarily of endogenous origin.

The rate of flux of cholesterol from plasma to aortic wall has been measured in normal and diabetic rats given an atherogenic diet. At any given time, there were significant linear relations between plasma cholesterol concentration and influx rate and between influx rate and aortic cholesterol concentration, These relationships altered with time in a manner to suggest the development of an inhibition to cholesterol influx. Diabetic animals had higher levels of plasma cholesterol, but the interdependencies among the three parameters noted were qualitatively the same as those of the nondiabetics, suggesting that the increased susceptibility of diabetics to the development of atherosclerosis is due to more severe hypercholesterolemia. The flux rate of cholesterol into the aorta was much higher than the net rate of cholesterol deposition, indicating that a large part of the influx is in the form of exchange with a labile pool. On replacement of the atherogenic diet by a normal diet, the plasma cholesterol fell promptly to normal while the aortic cholesterol fell more slowly and did not return to the normal level. The results applied equally to unesterified and total cholesterol and to cholesterol of whole plasma or low density lipoproteins.

The rate of growth of suckling rats can be greatly influenced by adjusting the size of the litter at birth. Even though ad lib. feeding be allowed after weaning at 21 days, the smaller rats from large litters become smaller adults than those whose development has been unrestricted in the suckling period. In rats the brain grows most actively and becomes myelinated during the second and third weeks of post-natal life while the animal is still suckling. Widdowson & McCance (i960), however, did not find that the weight of the brain was much affected by varying the plane of nutrition at this time. The experimental design of the previous authors was followed, and it was confirmed that varying the litter size during lactation made relatively little difference to the wet weight of the brain. There were, however, much larger differences in the rate of cholesterol deposition in the brain, and these were obtained with quite small alterations of body weight.

Summary Early atheromatous lesions were studied in femoral-popliteal and coronary arteries from a group of subjects aged 50–80 years. Macroscopic quantitation revealed a highly significant difference in the extent of such lesions; the femoral-popliteal arteries showed considerably more early lesions than did the coronaries. Four macroscopic types of early lesions were distinguished, each of them showed a characteristic histologic and histochemical pattern. The development of “preathe-romatous” lipid accumulation were more clearly revealed in the lower limb arteries, whereas coronary arteries displayed a more confused picture. Histochemically the pattern of phospholipid and cholesterol deposition in early femoral-popliteal lesions is the same as in other regions of the arterial tree. The presence of still active and evoluting atherosclerotic lesions in the arteries of old subjects supports the concept of atherosclerosis as a process that is repeatedly “re-awakening” or reactivated during life. This conclusion appears particularly relevant to the femoral-popliteal arteries.

THE rate of transfer of materials into the ovarian follicle is rapid (Knight and Schechtman, 1954), and it occurs at a non-linear rate (Warren and Conrad, 1939; Romanoff, 1943) which is maximum at about the 2.5 g. stage (Smith, 1959). These materials are synthesized, and transported from various sites in the body to the ovary. Chargaff (1942) reported that certain lipids are formed in the liver and are transported by the plasma to the ovary where deposition takes place. Popjak and Tietz (1953) have shown that the theca interna and granulosa, membranes surrounding the ovum, synthesize fatty acids and cholesterol in vitro from C14-labelled acetate. Indeed, Kritchevsky (1958) concluded that many tissues are capable of cholesterol synthesis in vitro among which are the liver, intestine, aorta, adrenal glands, gonads and brain. This evidence suggests that a very intricate system of synthesis and transportation of cholesterol to and across the follicular…

The observation that the myelin sheaths of human optic fibers seem to form first at the distal end of the tract with a progress of myelination toward the eye was tested by assays of cholesterol and cholesterol esters in segments of human optic nerves and tracts at various phases of development. It was found that the distal to proximal progress of myelination relates mainly to the fact that adult human optic fibers contain in their distal portion about twice the amount of cholesterol that occurs in the proximal portion. This gradient in cholesterol content along the fibers develops gradually in children. If the progress of cholesterol deposition is expressed as a percentage of the adult values, the proximo-distal differences are small, suggesting that myelination develops only slightly faster at the distal end.

The absence of chloroform-extractable cholesterol in submerged cultures or resting mycelial suspensions which were supplemented with the sterol is not evidence for metabolism of the substance by molds. Both broth cultures and washed mycelium of the molds used in these studies could make cholesterol un-extractable with chloroform. However, neither manometric studies using C414-cholesterol nor extensive steroid analyses revealed any products of cholesterol metabolism.Steroid uptake by washed cell preparations of these molds depends on the presence of a usable energy source or a high rate of endogenous respiration. Either starving or autoclaving destroyed the ability of washed mycelium to cause cholesterol to disappear from aqueous suspensions.Only a small fraction of the cholesterol removed from suspensions by the mycelium could be recovered by sonic vibration of the cells.

The disturbances in blood cholesterol level known to be associated with pregnancy, and the prevailing impression that pregnancy may increase the incidence of diseases associated with abnormal cholesterol deposition have indicated the desirability for study of the influence of cholesterol feeding during pregnancy.There is strikingly little record of such a study in the literature. Schonheimer1 reported that pregnant animals were more subject to the deposition of anisotropic fat than non-pregnant ones. He reports feeding cholesterol to a rabbit which became very sick 14 days after mating and showed resorption of 3 fetuses with one fetus dead at term and abnormal deposition of anisotropic fat in the placenta.We have used rats for the present study. These were placed at weaning on a diet made up of 20 parts raw casein, 4 parts Osborne and Mendel salts, 4 parts agar, 15 parts Crisco, and 57 parts starch, with one part cholesterol dissolved in Crisco and incorporated in the diet. Vitamin supplements were given ...

The lipotrophic activity of choline in experimental fatty cirrhosis of the liver, has been demonstrated by several groups of investigators.1,2,3 The possibility of similar action on other types of cholesterol deposition in other tissue, particularly in atheromatous lesions in the aorta, has suggested itself. The naturally occurring human-like subintimal aortic atheromatosis as reported by Dauber4a was chemically studied in 3-year-old certified 260 to 320 egg R.P.O. sired hens and the average level of certain chemical components established.4b The effect of choline on this pathological chemistry presented itself as an important problem.Steiner5 first and then Bauman and Rusch6 and about simultaneously Himsworth7 reported that they had not been able to demonstrate any action of choline on the high blood, aortic or liver content of cholesterol in cholesterol-fed rabbits. Andrews and Broun8 concluded that cholin protected against atherosclerosis and Huber, Broun, and Casey9 using lipocaic re ported the preven...