Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Guinea pigs were fed a semisynthetic diet containing 10% (by weight) cottonseed oil with or without 1% cholesterol. In response to cholesterol/fat feeding there was a significant accumulation of cholesteryl ester (CE), particularly in the liver, but also in the kidney, spleen and suprarenal glands. The hepatic acyl-CoA:cholesterol acyltransferase (ACAT) increased 5-10 times when the animals were fed cholesterol fat during 11 weeks while the acid cholesterol esterase (CE-ase) was similar in the two dietary groups. Intestinal lymph showed the highest content of cholesterol (both free and esterified) in guinea pigs fed cholesterol/fat. A low activity of lecithin:cholesterol acyltransferase (LCAT) was present in the intestinal lymph, irrespective of dietary composition. Triglyceride-rich lipoproteins seem to inhibit LCAT activity in the intestinal lymph. Plasma cholesterol levels in animals fed cholesterol/fat increased markedly while LCAT remained unaffected by the diets. Activity of ACAT and CE-ase in kidney and spleen was low compared to liver tissue and the enzyme activities were not affected by the cholesterol/fat feeding.
Atherosclerosis 1978 Jun
PMID:Cholesteryl ester metabolism in fat- and cholesterol/fat-fed guinea pigs. 67 14

Low levels of high-density lipoproteins have been consistently shown to be a major risk factor for coronary heart disease. However, the precise role of HDL in the prevention or reversal of atherosclerosis (or both) is unknown. It has been proposed that HDL functions jointly with the enzyme lecithin:cholesterol acyltransferase and the cholesteryl ester transfer protein to facilitate the movement of cholesterol from tissues to the liver. This mechanism--referred to as reverse cholesterol transport--has been shown to be an important physiologic mechanism. However, its clinical significance, though intriguing, is unclear. This article reviews recent advances concerning the components of reverse cholesterol transport and evaluates their potential significance in the early diagnosis and treatment of atherosclerosis.
 ...
PMID:Physiologic role and clinical significance of reverse cholesterol transport. 160 97

Eight patients with primary hypercholesterolemia were treated with probucol for 17 weeks. Plasma total cholesterol, low density lipoprotein (LDL)-cholesterol, and high density lipoprotein (HDL)-cholesterol decreased by 16.6, 15.0 and 25.7%, respectively, in response to probucol treatment. Plasma levels of apolipoprotein B and apolipoprotein A-I also decreased, while apolipoprotein A-II concentrations were unchanged. The decrease in HDL-cholesterol levels was associated with a reduction in HDL particle size. No changes in the plasma lecithin:cholesterol acyltransferase activity or mass occurred in response to probucol treatment. In contrast, a significant 25% increase in plasma cholesteryl ester and triglyceride transfer activity occurred following probucol treatment. There was a positive correlation (R = 0.94) between cholesterol ester and triglyceride transfer. We propose that the increase in lipid transfer activity may in part explain the changes in HDL concentration and size, as well as the previously reported effect probucol has on reducing atherosclerosis in animal models.
 ...
PMID:Effects of probucol on plasma lipids, lipoproteins and parameters of high density lipoprotein metabolism. 163 95

Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is a hereditary disorder with clinical manifestations including corneal opacity, premature atherosclerosis and renal failure. In this study, we analyzed the molecular base underlying a case of Japanese LCAT deficiency, in which both LCAT mass and activity of the proband were nearly absent. DNA blot hybridization analysis showed no gross rearrangement in the LCAT gene of the proband. The nucleotide sequence analysis of the cloned LCAT gene demonstrated only an extra nucleotide "C" insertion at the first exon, when compared to the sequence of wild type. This single base insertion caused a shift of the following reading frame, probably resulting in a truncated abnormal LCAT polypeptide that consist of only 16 amino acids. The direct sequence analysis of PCR-amplified DNA showed only the same insertion, indicating that the LCAT-deficient proband is a homozygote for the mutant allele. These results indicate that the clinical and biochemical feature of the patient is mainly caused by a complete deficiency of the enzyme based on a homozygous abnormality of LCAT gene.
 ...
PMID:Molecular defect in familial lecithin:cholesterol acyltransferase (LCAT) deficiency: a single nucleotide insertion in LCAT gene causes a complete deficient type of the disease. 166 3

Literature data suggest that identification of the conditions preventing lecithin:cholesterol acyltransferase (LCAT) to produce normal cholesterol esterification might be of utmost importance in the follow-up of atherosclerosis. Interrelationship between LCAT activity, and total cholesterol (TC), unesterified cholesterol (UC), esterified cholesterol (EC), low and high density lipoprotein cholesterol (LDL-C, HDL-C), triglycerides (TG), phospholipids (PL), free fatty acids (FFA), l-lactate (LAC), and electrolytes, i.e. zinc (Zn), calcium (Ca) and magnesium (Mg), was investigated in 60 patients with acute myocardial infarction (AMI), 30 patients with coronary heart disease (CHD) and 30 healthy control subjects. Results of the study revealed LCAT activity to be significantly decreased in atherosclerotic patients, with a significantly increased ratio of unesterified-esterified cholesterol (UC/EC), as compared to the control group of normal subjects. A decreased LCAT activity was accompanied by elevated values of phospholipids and LDL-C, a moderate increase in triglycerides, and a decreased quotient of HDL3/HDL2 cholesterol. Accordingly, a decreased activity of LCAT could with great certainty be considered a high-risk biochemical factor for atherosclerosis.
 ...
PMID:Lecithin:cholesterol acyltransferase activity in patients with acute myocardial infarction and coronary heart disease. 175 Aug 5

This review article attempts to present an overview of the occurrence and function of lipid storage and secretory organelles: the lamellar bodies. Morphologically these organelles vary considerably in size (100 nm to 2400 nm); they are surrounded by a membrane and contain multilamellar lipid membranes. Lamellar bodies may also contain apolipoproteins and lytic enzymes and have an acidic pH, which confers on them a lysosomal character. Under normal physiological conditions, the main function of lamellar bodies is the supply of extracellular domains with specialized lipid components related to a specialized function. The lamellar bodies of the lung epithelium are best investigated in their functional and structural features and are the storage form of the lung surfactant. They provide a monomolecular lipid film of dipalmitoyl phosphatidylcholine (DPPC) on the surface of lung alveoli to lower surface tension necessary for optimal gas exchange and a hydrophobic protective lining against environmental influences. Additional cells of the respiratory system such as the mucosa of the human nose and the bronchi contain lamellar bodies. Lamellar bodies are also found in the gastrointestinal tract, in tongue papillae, oral epithelium, and mucosa cells of the stomach. The major phospholipid of lamellar bodies in mucosa cells of the stomach is DPPC, providing a hydrophobic protective lipid film against the tissue-damaging activities of gastric juice. The hydrophobic water-protective barrier of the skin, which consists mainly of neutral lipids, however, also originates from lamellar bodies secreted by epithelial cells. Lamellar bodies, mainly consisting of DPPC, also occur in mesodermal cell layers of sliding surfaces to provide the lubrication of joints, of the peritoneum, pericardium, and pleural mesothelium. In certain pathological conditions, such as atherosclerosis, Niemann-Pick disease, lecithin:cholesterol acyltransferase (LCAT) deficiency, cholestasis, degeneration of nerves and brain, and regeneration of nerves and wound healing, lipid-containing lamellar bodies have been observed in various cells, the function of which still remains to be elucidated. In early and late lesions of atherosclerotic plaques, lamellar bodies, consisting of unesterified cholesterol and phospholipids, are associated with the extracellular matrix of the intima. During regression of fatty streaks, lamellar bodies are seen intracellularly in macrophages and smooth muscle cells. Inherited metabolic disorders, such as Niemann-Pick disease type I and type II, result in the excessive accumulation of lamellar body-containing cells, for example in bone marrow, spleen, and lymphoid tissue. Type I is a deficiency in sphingomyelinase and type II is a defect in intracellular trafficking of lipoprotein-derived cholesterol.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Structure and function of lamellar bodies, lipid-protein complexes involved in storage and secretion of cellular lipids. 179 38

The effect of drinking pattern on plasma lipoproteins and body weight was examined in three groups of squirrel monkeys: (1) controls fed isocaloric liquid diet; (2) regular drinkers given liquid diet containing ethanol (EtOH) substituted isocalorically for carbohydrate at 12% of calories daily; and (3) binge drinkers fed 6% EtOH calories daily for a four-day period followed by three days of 20% EtOH to mimic a weekend bout drinking cycle. The number of calories offered per day was the same for all groups, and the average weekly EtOH consumption (12% calories) was identical for the two alcohol treatments. The entire study lasted six months. There were no significant differences in plasma cholesterol, triglyceride or liver function tests. Regular drinkers had the highest high density lipoprotein2/high density lipoprotein3 (HDL2/HDL3) protein and apolipoprotein A-I/B ratios of any group and exhibited a significant elevation in the molar plasma lecithin:cholesterol acyltransferase (LCAT) rate (nmol/min/ml). Binge drinking produced a selective increase in low density lipoprotein (LDL) cholesterol and apolipoprotein B, and a depression in the fractional LCAT rate (% esterified/min). During the course of the study, controls ate 92% of their diet while the alcohol groups each consumed 95% of the liquid diet. Despite this difference, body weight and Quetelet index (weight/height2) decreased progressively in the order controls greater than regular drinkers greater than binge drinkers. Results from our study indicate that moderate, regular daily consumption of EtOH at 12% of calories causes a modest reduction in body weight and produces a coronary protective lipoprotein profile (increases HDL2/HDL3, increases apolipoprotein A-I/B, low LDL cholesterol). By contrast, when this same average weekly dose is concentrated in a binge cycle, unfavorable alterations in lipoprotein composition (increases LDL cholesterol, increases apolipoprotein B) and metabolism (decreases LCAT activity) occur along with weight loss and depletion of body fat. These studies point to the value of the squirrel monkey model in evaluating both favorable and pathophysiological effects of chronic EtOH intake.
Atherosclerosis 1991 May
PMID:Effect of drinking pattern on plasma lipoproteins and body weight. 187 9

The purpose of this symposium was to provide a forum for the reporting of recent findings and the exchange of ideas concerning reverse cholesterol transport, an area of intense interest and some controversy. Data from epidemiological studies have consistently shown that elevated levels of high density lipoproteins (HDL) are an index of increased protection against coronary heart disease. However, the mechanism whereby HDL is involved in the prevention and/or reversal of atherosclerosis is unknown. According to one of the hypotheses, HDL acts as the primary acceptor of unesterified cholesterol from cells and functions jointly with the enzyme lecithin:cholesterol acyltransferase (LCAT) and the cholesteryl ester transfer protein (CETP) to facilitate the movement of cholesterol from peripheral tissues to the plasma and ultimately to the liver. Although this mechanism as originally proposed by Glomset is an essential physiological mechanism, the clinical significance of this hypothesis remains unsubstantiated. Key elements of knowledge are lacking that would allow the linking of cholesterol efflux from cells and tissues with specific events in HDL metabolism, particularly those that are relevant to the prevention and/or reversal of atherosclerosis. Because of the intricate nature of the interaction between the components of reverse cholesterol transport, a conference involving the leading investigators of the field, where extensive discussion of the findings and ideas is allowed, appeared highly desirable. Indeed, from the distance of nearly 4 months, feedback from the participants indicates that the meeting was highly successful and the organizers feel that all the projected goals of the symposium were accomplished.
 ...
PMID:International Symposium on Reverse Cholesterol Transport. Report on a meeting. 198 32

Mouse plasma from strains C57BL/6J and C3H/HeJ includes a high density lipoprotein (HDL) fraction containing apolipoprotein A-I which migrates in the prebeta region upon agarose gel electrophoresis, similar to the prebeta HDL previously reported in humans. This prebeta A-I lipoprotein species has a buoyant density of 1.080-1.210 g/ml and has two molecular weight species, 65,000 and 71,000. It is lipid-poor and deficient in apolipoprotein E. When mice are fed a high fat and high cholesterol diet, the quantity of prebeta A-I increases in both strains as determined by quantitative densitometry of agarose gel immunoblots. Prebeta A-I species are highly unstable in plasma at 37 degrees C. Initially (0-1 h) levels decreased and with further incubation (1-8 h) levels increased. Nondenaturing polyacrylamide gel electrophoresis (PAGE) demonstrated that the prebeta HDL formed during prolonged incubation (1-8 h) was identical in size to HDL in unincubated samples. The initial decrease of prebeta HDL observed during the first hour of incubation, phase I, was inhibited by DTNB, suggesting that phase I is dependent on lecithin:cholesterol acyltransferase (LCAT); however, the subsequent increase, phase II, was unaffected by DTNB and appears LCAT-independent. The prebeta A-I species formed in plasma containing DTNB after a 4-h incubation resulted in a polydisperse particle size distribution. The two strains, the atherosclerosis-susceptible C57BL/6 and -resistant C3H, displayed a similar elevation and induction of prebeta HDL during a dietary switch from laboratory chow to an atherogenic diet with a transient peak occurring at 7 days even when total HDL in the susceptible strain was greatly reduced.
 ...
PMID:Interconversion of prebeta-migrating lipoproteins containing apolipoprotein A-I and HDL. 210 30

The relationships between plasma lecithin:cholesterol acyltransferase (LCAT) mass concentrations and lipids, apolipoprotein, and lipoprotein subfraction concentrations were studied in men assigned at random to a one-year exercise program (n = 48) and to a sedentary control condition (n = 31). Exercise training did not significantly affect mean concentrations of LCAT-mass. Moreover changes in LCAT within the exercise group were unrelated to distance run and weight loss. The baseline data and the one-year change data showed consistent positive correlations between LCAT concentrations and total cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, and apolipoprotein B concentrations, and consistently weak correlations between LCAT concentrations and high density lipoprotein (HDL)-cholesterol, HDL2, and apolipoprotein A-I concentrations. The strong correlation between LCAT and total cholesterol may account for LCAT's relationships with lipoprotein subfractions, apolipoprotein B and other lipoprotein cholesterol concentrations.
Atherosclerosis 1990 May
PMID:Associations of lecithin: cholesterol acyltransferase (LCAT) mass concentrations with exercise, weight loss, and plasma lipoprotein subfraction concentrations in men. 236 Sep 20


1 2 3 4 5 6 7 8 9 10 Next >>