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)

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.
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PMID:Physiologic role and clinical significance of reverse cholesterol transport. 160 97

Cholesteryl ester transfer protein may play a role in the cholesteryl ester metabolism between high density lipoproteins (HDL) and apolipoprotein B-containing lipoproteins. To investigate relationship between HDL and cholesteryl ester transfer protein (CETP) activity in the development of atherosclerosis, the present study has focused on CETP activity in the patients with familial hypercholesterolemia (GH). HDL-C and HDL-C/apo A-I mass ratio in heterozygous FH were lower than those in normolipidemic controls. There was a 2-fold increase in total CETP activity in incubated FH serum compared with normolipidemic controls. Assays for CETP activity in the lipoprotein deficient serum (d greater than 1.215 g/ml) were carried out by measuring the transfer of radioactive cholesteryl ester from HDL (1.125 less than d less than 1.21 g/ml) to LDL (1.019 less than d less than 1.060 g/ml). CETP activities in heterozygous FH (79 +/- 4 nmol/ml/h) was significantly higher than those in normolipidemic controls (54 +/- 6 nmol/ml/h). The increased total cholesteryl ester transfer mainly results from increased CETP activity in the d greater than 1.215 g/ml, possibly reflecting an increase in CETP mass in serum. Increased CETP activity in the d greater than 1.215 g/ml was correlated positively with IDL-cholesterol/triglyceride mass ratio (r = 0.496, p less than 0.01), and negatively with HDL-cholesterol/apo A-I mass ratio (r = -0.334, p less than 0.05). These results indicate that the enhanced CETP activities may contribute to increase risk for developing atherosclerosis in FH by changing the distribution of cholesteryl ester in serum lipoproteins.
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PMID:Enhanced cholesteryl ester transfer protein activities and abnormalities of high density lipoproteins in familial hypercholesterolemia. 163 94

Activities of cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) were measured in plasma of four vertebrate species: man, rabbit, pig, and rat. The activities were measured in the absence and presence of antibodies raised against purified human CETP. PLTP activities were present in all four species with highest values in pig (11.7 +/- 1.2 U/ml) and human plasma (9.2 +/- 1.6 U/ml). Considerable lower activities were found in rabbit (3.5 +/- 0.6 U/ml) and rat plasma (1.6 +/- 0.7 U/ml). These activities were not affected significantly by antibody against human CETP. CETP activities could be measured in human (0.23 +/- 0.05 U/ml) and in rabbit plasma (0.19 +/- 0.03 U/ml). CETP activity in human plasma was inhibited over 97% by antibody against human CETP. Plasma was chromatographed on a Superose 6 gel filtration column. Average HDL particle sizes in the four species differed notably and decreased in the order: rat HDL greater than rabbit HDL greater than human HDL greater than pig HDL. A separation of the two lipid transfer activities was evident after gel filtration chromatography. The peak of the PLTP activity coeluted with a fraction of HDL particles with the size of human HDL2 (particle weights 300-375 kDa). CETP activity in human and rabbit plasma coeluted largely with relatively small HDL particles (particle weights 140-180 kDa). These results show that CETP and PLTP activities are located in different macromolecular complexes.
Atherosclerosis 1991 Oct
PMID:Different locations of cholesteryl ester transfer protein and phospholipid transfer protein activities in plasma. 175 86

Studies were performed to investigate the effect of diets rich in oleic or linoleic acids on the activity of plasma cholesteryl ester transfer protein (CETP) in normolipidemic subjects. Previous to the test diets, all subjects consumed a baseline diet rich in saturated fatty acids ("sat-diet") for 17 days. The test diets, rich in either monounsaturated fatty acids ("mono-diet") or rich in polyunsaturated fatty acids ("poly-diet"), were given for 5 weeks to 52 normolipidemic healthy volunteers. The activity of CETP was measured, using a method independent of endogenous plasma lipoproteins, as the rate of exchange of radioactive cholesteryl oleate between labelled LDL and unlabelled HDL. The "mono-diet" induced a statistically significant decrease in CETP activity (from 115 +/- 20 to 102 +/- 19 units/ml plasma, P less than 0.01), while the small decrease on the "poly-diet" (from 111 +/- 23 to 107 +/- 22 units/ml plasma) did not reach significancy. The percentual decrease in CETP activity induced by the "mono-diet" was higher than that induced by the "poly-diet" as was also found for the decrease in LDL cholesterol. In both diet groups a positive correlation was found between changes in CETP activity and changes in plasma total or (VLDL + LDL) cholesterol. The results suggest that high levels of dietary monounsaturated fatty acids may result in decreased plasma CETP activity, as well as LDL cholesterol levels. The mechanisms of these effects, and their possible interrelations, remain to be established.
Atherosclerosis 1991 Apr
PMID:Diet-induced alteration in the activity of plasma lipid transfer protein in normolipidemic human subjects. 185 68

Reverse cholesterol transport identifies a series of metabolic events resulting in the transport of cholesterol from peripheral tissues to the liver and plays a major role in maintaining cholesterol homeostasis in the body. High density lipoproteins (HDL) are the vehicle of cholesterol in this reverse transport, a function believed to explain the inverse correlation between plasma HDL levels and atherosclerosis. An attempt to stimulate, by the use of drugs, this transport process seems to be of great promise in the prevention and treatment of arterial disease. Only few drugs are now known that can modify the activity of the various factors involved in the process. Clofibrate reduces cholesterol esterification, but the newer fibric acids are generally ineffective as anion-exchange resins. Probucol directly increases the activity and mass of cholesteryl ester transfer protein, thus possibly improving the physiological process of cholesterol removal from tissues. The few available data on the effects of drugs on reverse cholesterol transport should stimulate the search for new agents specifically stimulating this antiatherogenic process.
Atherosclerosis 1991 Jun
PMID:Reverse cholesterol transport: physiology and pharmacology. 189 92

A cDNA clone containing the coding region for cynomolgus monkey cholesteryl ester transfer protein (CETP) was isolated by the polymerase chain reaction with primers based on the human CETP cDNA sequence and cDNA synthesized from liver poly (A+) RNA. Analysis of that cDNA indicated that the nucleotide and amino acid sequences of cynomolgus monkey CETP were greater than 95% homologous with the human sequences. A fragment of the cDNA was used to develop an internal-standard/RNAse protection assay that allowed precise quantification of CETP mRNA levels. Analysis of total RNA from various tissues with this assay revealed that the liver and thoracic aorta expressed high levels of CETP mRNA; the mesenteric fat, adrenal gland, spleen, and abdominal aorta had low but detectable levels of the mRNA; and the brain, kidney, intestine, and skeletal muscle had undetectable levels of that mRNA. When the monkeys were made hypercholesterolemic by a high-fat, high-cholesterol (HFHC) diet, hepatic levels of CETP mRNA increased from 1.6 +/- 0.4 pg/micrograms total RNA (mean +/- SEM) to 4.1 +/- 0.8 pg/micrograms (p less than 0.005); mesenteric fat CETP mRNA increased from 0.4 +/- 0.1 pg/micrograms total RNA to 5.3 +/- 2.2 pg/micrograms (p less than 0.05); and plasma CET activity increased approximately fourfold. The CETP mRNA levels in the thoracic and abdominal aortas were not significantly increased in monkeys fed the HFHC diet, even though those animals had gross atherosclerosis. The apoprotein E mRNA levels, however, were markedly increased in the aortas of monkeys with atherosclerosis, with the largest increase occurring in the abdominal aorta. Taken together, these data suggest that lipid deposition in the artery was not accompanied by increased expression of the CETP gene in that tissue. Statistical analysis showed that a strong, negative correlation existed between hepatic CETP mRNA levels and both high density lipoprotein cholesterol (r = -0.85, p less than 0.001) and apoprotein A-I (r = -0.84, p less than 0.001). These data suggest that HFHC diet-induced changes in high density lipoprotein metabolism may be linked to altered expression of a function CETP gene.
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PMID:Molecular cloning, sequence, and expression of cynomolgus monkey cholesteryl ester transfer protein. Inverse correlation between hepatic cholesteryl ester transfer protein mRNA levels and plasma high density lipoprotein levels. 193 78

The influence of variation in the genes for cholesteryl ester transfer protein and apolipoprotein A-I was investigated in 95 patients with coronary heart disease and 95 matched control subjects of South East Asian extraction. Restriction fragment length polymorphisms (RFLPs) linked to the cholesteryl ester transfer protein gene TaqIA and TaqIB, and to the apolipoprotein A-I gene SstI, were examined to investigate the extent of genetic variation at these loci. None of the alleles defined by these RFLPs were associated with increased coronary risk. Analysis of the data by division of high density lipoprotein-cholesterol levels into tertiles showed a trend of a higher frequency of B1 allele (presence of the TaqIB site) with reduced high density lipoprotein levels. The B1 allele was more frequent in control subjects, with low high density lipoprotein levels (P less than 0.02), but not in coronary heart disease patients. The differences became significant for both groups (P less than 0.05) when the data of non-smokers were analysed separately.
Atherosclerosis 1990 Jul
PMID:Genetic variation in the cholesteryl ester transfer protein and apolipoprotein A-I genes and its relation to coronary heart disease in a Sri Lankan population. 197 78

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.
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PMID:International Symposium on Reverse Cholesterol Transport. Report on a meeting. 198 32

This study was undertaken to determine potential tissue sources of plasma cholesteryl ester transfer protein (CETP), and to assess the influence of CETP on lipoprotein concentrations and atherosclerosis. In a group of 28 cynomolgus monkeys fed high fat, high cholesterol diets, plasma CETP concentration was strongly correlated with the abundance of CETP mRNA in liver and in adipose tissue, and with the output of CETP in liver perfusates. Plasma CETP concentration showed a strong inverse correlation with HDL cholesterol concentrations (r = -0.62, P less than 0.001) and a positive correlation with LDL cholesterol concentration (r = 0.54, P less than 0.005) and molecular weight (r = 0.57, P less than 0.001). The extent of coronary artery atherosclerosis was positively correlated with LDL cholesterol concentration and molecular weight, and with plasma CETP concentration. Thus, in monkeys fed an atherogenic diet, individual variation in CETP mRNA abundance in liver and adipose tissue probably plays a major role in the determination of plasma CETP levels. In plasma, CETP influences the distribution of cholesteryl esters between LDL and HDL, and CETP concentration appears to be a key determinant of the relative atherogenicity of the plasma lipoproteins.
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PMID:Plasma lipid transfer protein as a determinant of the atherogenicity of monkey plasma lipoproteins. 202 28

The biochemical basis for the apparent deficiency of cholesteryl ester (CE) transfer activity was investigated in two unrelated subjects with markedly elevated high density lipoprotein-cholesterol (Atherosclerosis 1988; 70:7-12). Essentially no CE or triglyceride transfer activity was detected in the patients' plasma, utilizing four different lipid transfer assays. Using polyclonal antibodies raised against human plasma cholesteryl ester transfer protein (CETP), a delayed-addition enzyme immunoassay was developed to determine plasma CETP mass. CETP could not be detected with this assay in the plasma of the two subjects with transfer activity deficiency, indicating that the CE transfer activity deficiency in these subjects is due to the absence of plasma CETP. In addition, three hyperalphalipoproteinemic subjects with a partial deficiency of CE transfer activity had a reduced level of CETP mass. There was a good correlation between plasma CETP activity and mass levels. The principles of this immunoassay may be applicable to measure the mass levels of other proteins with catalytic activities.
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PMID:A delayed-addition enzyme immunoassay for the relative cholesteryl ester transfer protein mass in patients with deficient plasma cholesteryl ester transfer activity. 209 68


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