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

In cardiovascular diseases with potential atherosclerosis, the serum concentration of HDL cholesterol as determined by a precipitation method with dextran sulfate and Mg++ was lower while that of total cholesterol was normal or elevated. Treatment with a daily dose of 1,200 mg of Nicomol, a derivative of nicotinic acid, for 1 to 3 months increased the mean HDL cholesterol level by 3 to 5 mg/dl and reduced the total cholesterol level by 14 to 15 mg/dl and total/HDL cholesterol ratio by 0.8 (3 months) to 0.9 (1 month, p less than 0.05). Similar decreases in HDL cholesterol concentration were also found in parenchymal and obstructive liver diseases with normal total cholesterol values except in fulminant hepatitis and intrahepatic cholestasis.
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PMID:Effect of nicomol on HDL cholesterol level. 22 32

A wide-range complex of biochemical techniques was used to study metabolic processes in workers exposed to cobalt and ethanol. In practically healthy workers were found laboratory manifestations of hepato-biliary irritations, hyperpermeability of the hepatocytes' cytoplasmic membrane, cholestasis syndrome, initial manifestations of muscular dystrophy and minor signs of atherosclerosis risks. The biochemical shifts were like those in alcoholism cases. It was suggested that, under the existing technological conditions of cobalt-containing hard-facing alloys' powder processing, the action of ethanol increased the toxic effect of cobalt.
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PMID:[Metabolic status in workers engaged in the production of cobalt-containing powder compositions of hard alloys]. 179 96

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)
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PMID:Structure and function of lamellar bodies, lipid-protein complexes involved in storage and secretion of cellular lipids. 179 38

Extrahepatic biliary obstruction in humans and rats leads to hypertriglyceridemia. The observed hypertriglyceridemia could result from either a defect of plasma triglyceride (TG) catabolism or hepatic over-production of TG. To examine these questions we have used the rat model to determine hepatic TG secretion by the Triton WR-1339 methodology (inhibition of peripheral lipolysis) and exogenous TG clearance (after i.v. injection of Intralipid). Four groups of rats were studied: group OB--48 h post-operative--bile-duct obstructed; group DV--bile diverted; group SC--sham-operated controls; and group FC--48 h fasted, unoperated controls. The hepatic TG secretion rate for group OB rats was a factor of 7 lower than that of either group SC or FC, and 5 times lower than that for group DV. There were no differences between the hepatic TG secretion rates of groups DV and FC or SC. After i.v. injection of Intralipid, plasma TG decreased with first-order kinetics. The rate constant was taken as the exogenous TG clearance rate (ETGCR). Mean ETGCR for group OB was a factor of 3 lower than that for either control group; while the ETGCR for group DV was equivalent to the control groups. Thus biliary diversion does not affect hepatic TG secretion or the ETGCR. The apparent cause of the hypertriglyceridemia of cholestasis in the bile-obstructed rat is impaired plasma TG catabolism.
Atherosclerosis 1987 Apr
PMID:Inhibition of hepatic triglyceride secretion and exogenous triglyceride clearance in the cholestatic rat. 360 11

To study the effect of hemodialysis on serum lipids and lipoproteins, five patients with normal renal function who had undergone hemodialysis for schizophrenic symptoms for 10 weeks in a crossover study were investigated. Active or sham (no dialysate flow through the filter) dialysis was instituted randomly. Serum lipids were isolated by ultracentrifugation and precipitation before and after each period. High density lipoprotein (HDL) cholesterol levels were constantly low and correlated negatively with serum alkaline phosphatase concentrations (p less than 0.05). Serum and very low density lipoprotein (VLDL) triglycerides and VLDL cholesterol increased during active, and to a lesser extent during sham, dialysis. Dialysis of this intensity does not affect HDL. The low levels may be secondary to subclinical cholestasis from neuroleptic drug treatment. Some individuals may develop hypertriglyceridemia of unknown pathogenesis during hemodialysis. Both these lipoprotein abnormalities are risk factors for the development of atherosclerosis.
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PMID:Serum lipids and lipoproteins in schizophrenic patients with normal renal function treated with hemodialysis. 657 52

The disturbance of lipid metabolism is seen in some inherited diseases and also in patients with some kinds of underlying diseases. The presence of its disturbance can be detected by measuring the concentrations of cholesterol and triglyceride in serum. Although hyperlipidemia or hypolipidemia is the result of abnormal lipid metabolism, hyperlipidemia is of more concern to physicians because of the close association with atherosclerosis. Responsible genes for some primary (or hereditary) hyperlipidemic diseases have been confirmed as follows; LPL or apo C-II for primary chylomicronemia, LDL receptor for familial hypercholesterolemia and apo B-100 for familial defective apo B-100. However, the responsible gene remains controversial for familial combined hyperlipidemia, though AI/CIII/AIV cluster is one of the possible candidate genes. Secondary hyperlipidemia is caused by various diseases such as diabetes mellitus, renal diseases and cholestasis. This type of hyperlipidemia is improved by therapy for the underlying diseases. To date, the mechanism of lipid metabolism has been defined in a molecular basis. In fact, sterol regulatory element-binding protein (SREBP), peroxisome proliferator-activated receptor (PPAR) and ATP-binding cassette transporter subfamily A, member 1(ABCA1) were recently identified and it was demonstrated that these regulate lipid metabolism.
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PMID:[Disturbance of lipid metabolism]. 1198 47

A genome scan performed on 648 pedigreed baboons to detect and localize quantitative trait loci (QTL) for lipoprotein phenotypes that are known risk factors for atherosclerosis indicated the presence of a QTL on chromosome 18q that exerts a major influence on HDL-cholesterol (HDL-C) related phenotypes. Inspection of the human gene map revealed that the familial intrahepatic cholestatis gene 1 (FIC1) maps to the homologous region of baboon chromosome 18 containing the major QTL influencing HDL-C phenotypes. FIC1 is a strong biological candidate for this QTL because HDL-C is the preferred precursor for bile acid synthesis. In this study, we cloned and sequenced FIC1 cDNA and found that it is highly conserved between human and baboon. We also sequenced FIC1 cDNAs from a panel of unrelated baboons revealing single nucleotide polymorphisms (SNPs) and a polymorphic dinucleotide repeat. None of the baboon SNPs corresponded to human FIC1 mutations associated with familial intrahepatic cholestasis or benign recurrent intrahepatic cholestasis disorders.
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PMID:The FIC1 gene: structure and polymorphisms in baboon. 1207 45

Mice with homozygous null mutations in the high-density lipoprotein receptor SR-BI (scavenger receptor class B, type I) and apolipoprotein E genes fed a low-fat diet exhibit a constellation of pathologies shared with human atherosclerotic coronary heart disease (CHD): hypercholesterolemia, occlusive coronary atherosclerosis, myocardial infarctions, cardiac dysfunction (heart enlargement, reduced systolic function and ejection fraction, and ECG abnormalities), and premature death (mean age 6 weeks). They also exhibit a block in RBC maturation and abnormally high plasma unesterified-to-total cholesterol ratio (0.8) with associated abnormal lipoprotein morphology (lamellar/vesicular and stacked discoidal particles reminiscent of those in lecithin/cholesterol acyltransferase deficiency and cholestasis). Treatment with the lipid-lowering, antiatherosclerosis, and antioxidation drug probucol extended life to as long as 60 weeks (mean 36 weeks), and at 5-6 weeks of age, virtually completely reversed the cardiac and most RBC pathologies and corrected the unesterified to total cholesterol ratio (0.3) and associated distinctive abnormal lipoprotein morphologies. Manipulation of the timing of administration and withdrawal of probucol could control the onset of death and suggested that critical pathological changes usually occurred in untreated double knockout mice between approximately 3 (weaning) and 5 weeks of age and that probucol delayed heart failure even after development of substantial CHD. The ability of probucol treatment to modulate pathophysiology in the double knockout mice enhances the potential of this murine system for analysis of the pathophysiology of CHD and preclinical testing of new approaches for the prevention and treatment of cardiovascular disease.
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PMID:Probucol prevents early coronary heart disease and death in the high-density lipoprotein receptor SR-BI/apolipoprotein E double knockout mouse. 1277 86

Alagille syndrome (AGS) is a rare hereditary disorder exhibiting fluctuating cholestasis and dyslipidemia. Farnesoid X receptor (FXR) and liver X receptor (LXR) are hepatic nuclear receptors that regulate bile acid and lipoprotein metabolism. To investigate whether cholestasis is related to dyslipidemia and hepatic nuclear receptor expression in AGS patients, we determined the blood levels of total bile acid (TBA) and lipoprotein parameters, and examined hepatic nuclear receptor expression in three AGS children and their three incomplete AGS parents repeatedly over several years. In the AGS children, TBA level showed significant positive correlations with low-density lipoprotein-cholesterol, apolipoprotein E (apoE)-rich high-density lipoprotein-cholesterol (HDL-C), apoA-I, apoE, and cholesteryl ester transfer protein (CETP) concentrations, but negative correlation with apoE-poor HDL-C concentration. Western blot analysis of liver biopsy specimens revealed that FXR and LXR expression increased in parallel with TBA level. CETP- and ATP-binding cassette transporter A1 expression also increased with TBA level, while scavenger receptor class B type-I expression showed the opposite response. However, apoA-I expression was similar to the control level at any TBA level. In the incomplete AGS parents, TBA and lipoprotein parameters showed little fluctuation. In summary, cholestasis is closely related to dyslipidemia and hepatic nuclear receptor expression in AGS patients.
Atherosclerosis 2008 Jun
PMID:Fluctuation of lipoprotein metabolism linked with bile acid-activated liver nuclear receptors in Alagille syndrome. 1843 Apr 27

Cerebrotendinous xanthomatosis (CTX) OMIM#213700 is a rare disorder of bile acid synthesis caused by deficiency of the enzyme sterol 27-hydroxylase. It results in deficiency of bile acids and accumulation of abnormal bile alcohols and accelerated cholesterol synthesis. CTX usually presents in the second or third decade with slowly progressive neurological dysfunction, cerebellar ataxia and premature atherosclerosis. Treatment with bile acid supplementation improves but does not completely reverse the neurological signs and symptoms. However, CTX is now known to be associated with a period of neonatal cholestasis. If it is diagnosed at this point, treatment may prevent the onset of neurological problems. We present the case histories and developmental findings in two affected siblings treated from infancy. We plan to continue regular neurodevelopmental reviews.
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PMID:Prospective treatment of cerebrotendinous xanthomatosis with cholic acid therapy. 1912 50


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