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)

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

Transfers or exchanges of cholesterol esters and triglycerides between lipoproteins are mediated by a specialized protein referred to as cholesteryl ester transfer protein (CETP), whereas those of phospholipids (PLs) are facilitated by both CETP and a specific phospholipid transfer protein (PLTP). In the present study, the authors compared phospholipid transfer (PLT) in normal subjects and in patients with non-insulin-dependent diabetes (NIDD), which is associated with an increased risk of atherosclerosis. PLT was measured in different recombination experiments using an isotopic assay in which the transfer of labelled PLs from very low-density lipoprotein (VLDLs) and low-density lipoproteins (LDLs) to high-density lipoproteins (HDLs) was determined. This allowed discrimination between the roles of VLDLs + LDLs, HDLs, and plasma PLT activity (PLTA). VLDL + LDL-dependent PLT, HDL-dependent PLT and PLTA were decreased in NIDD. VLDL + LDL-dependent PLT was found to be negatively correlated with the PL/apolipoprotein B ratio, whereas HDL-dependent PLT was positively correlated with the HDL2/HDL3 and PL/apolipoprotein A-I ratios and negatively correlated with the flow activation energy at the HDL surface. The HDL2/HDL3 ratio was positively correlated with PLTA but not with CETP, which confirms previous reports suggesting that PLTP might act as an HDL conversion factor. These data show that several abnormalities in PLT occur in NIDD and raise the question as to whether a lowered PLT might be a new characteristic of dis factors associated with an increased risk of atherosclerosis.
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PMID:Multiple abnormalities in the transfer of phospholipids from VLDL and LDL to HDL in non-insulin-dependent diabetes. 890 50

The role of plasma phospholipid transfer protein (PLTP) in lipoprotein metabolism is poorly understood. In vitro studies suggest that PLTP influences HDL size and composition and transfers phospholipids among lipoproteins. To provide an in vivo model for studies of PLTP physiology, transgenic mice that express human PLTP were generated. Human PLTP transcripts were detected in total RNA from adipose tissue, lung, heart, and spleen of the two distinct lines (A and C) of transgenic mice. Despite minimal expression of human PLTP in the liver of these transgenic mice and similar plasma phospholipid transfer activity in transgenic and non-transgenic mice (19.1 +/- 3.1 vs 18.9 +/- 2.7 mumol/ml/h), differences in lipoprotein levels were observed between transgenic and control mice receiving the same chow diet. Male transgenic mice of line C had significantly higher HDL cholesterol than control mice (76.4 +/- 4.6 vs 71.9 +/- 7.0 mg/dl, p < 0.05) and the male transgenic mice of lines A and C had a significantly lower non-HDL cholesterol (15.1 +/- 4.1 and 15.6 +/- 4.7 vs 20.9 +/- 5.5 mg/dl, P < 0.01 and P < 0.02) and a significantly higher HDL cholesterol/non-HDL cholesterol ratio than the control mice (5.3 +/- 1.3 and 5.5 +/- 2.2 vs 3.9 +/- 1.9 mg/dl, P < 0.01 and P < 0.02). Female mice from transgenic line C had higher HDL cholesterol than control mice (64.6 +/- 4.8 vs 57.4 +/- 5.1 mg/dl, P < 0.01) while female mice from line A tended to have higher HDL cholesterol/non-HDL cholesterol ratio than control mice (5.5 +/- 3.7 vs 3.8 +/- 1.4). These observations suggest that expression of PLTP in peripheral tissues play an important role in lipoprotein metabolism. Expression of human PLTP produced a more favorable lipoprotein profile and thus, enhanced expression of PLTP could potentially retard atherosclerosis.
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PMID:Transgenic mice expressing human phospholipid transfer protein have increased HDL/non-HDL cholesterol ratio. 900 18

We measured the capacity of human plasma to induce cholesterol efflux from Fu5AH rat hepatoma cells in four groups of men with or without non-insulin-dependent diabetes mellitus (NIDDM) and coronary artery disease (CAD). Plasma from men with both NIDDM and CAD (n = 47) had the lowest efflux capacity (17.3 +/- 3.6%) whereas healthy control subjects with neither diabetes nor CAD (n = 25) had the highest capacity (19.8 +/- 3.4%). The groups with CAD but no diabetes (n = 44) and with NIDDM but no CAD (n = 35) had intermediate efflux values (18.5 +/- 3.8 and 18.5 +/- 3.9%, respectively). In a 2 x 2 factorial ANOVA, the differences were significant with respect to the presence of CAD (P = 0.038) and NIDDM (P = 0.041), with no interaction between the factors. The concentration of HDL particles containing apolipoprotein (apo) A-I but no apo A-II (LpA-I) was not related to efflux capacity in univariate or multivariate analyses. A multivariate regression analysis showed that when controlled for the presence of NIDDM and CAD, the concentration of particles containing both apo A-I and apo A-II (LpA-I:A-II) and plasma phospholipid transfer protein activity were both positively, independently, and significantly (P < 0.001) related to cholesterol efflux capacity.
Atherosclerosis 1996 Dec 20
PMID:Cholesterol efflux from Fu5AH hepatoma cells induced by plasma of subjects with or without coronary artery disease and non-insulin-dependent diabetes: importance of LpA-I:A-II particles and phospholipid transfer protein. 912 15

Cafestol and kahweol-diterpenes present in unfiltered coffee-strongly raise serum VLDL and LDL cholesterol and slightly reduce HDL cholesterol in humans. The mechanism of action is unknown. We determined whether the coffee diterpenes may affect lipoprotein metabolism via effects on lipid transfer proteins and lecithin:cholesterol acyltransferase in a randomized, double-blind cross-over study with 10 healthy male volunteers. Either cafestol (61-64 mg/day) or a mixture of cafestol (60 mg/day) and kahweol (48-54 mg/day) was given for 28 days. Serum activity levels of cholesterylester transfer protein, phospholipid transfer protein and lecithin:cholesterol acyltransferase were measured using exogenous substrate assays. Relative to baseline values, cafestol raised the mean (+/- S.D.) activity of cholesterylester transfer protein by 18 +/- 12% and of phospholipid transfer protein by 21 +/- 14% (both P < 0.001). Relative to cafestol alone, kahweol had no significant additional effects Lecithin:cholesterol acyltransferase activity was reduced by 11 +/- 12% by cafestol plus kahweol (P = 0.02). It is concluded that the effects of coffee diterpenes on plasma lipoproteins may be connected with changes in serum activity levels of lipid transfer proteins.
Atherosclerosis 1997 Jul 25
PMID:The cholesterol-raising diterpenes from coffee beans increase serum lipid transfer protein activity levels in humans. 924 72

High density lipoprotein 2 (HDL2) was incubated with phospholipid transfer protein (PLTP) or with hepatic lipase (H-TGL), and the incubation products were separated into a d < 1.22 g/ml and a d > 1.22 g/ml fractions. The d < 1.22 g/ml fraction produced by PLTP was larger, had lower apolipoprotein A-I and higher lipid and apolipoprotein A-II content than native HDL2. The d > 1.22 g/ml fraction represented 30% of the initial HDL2 protein and consisted of small, apolipoprotein A-I and phospholipid-rich particles, with a high sphingomyelin:phosphatidylcholine ratio. Incubation with H-TGL led to a d < 1.22 g/ml fraction which was comparable to native HDL2 regarding size and chemical composition. The d > 1.22 g/ml particles represented only 5% of the initial HDL2 protein and had slightly higher diameter and sphingomyelin:phosphatidylcholine ratio than those produced by PLTP. Enrichment of HDL2 with triglyceride prior to incubation increased the amount of protein released into the d > 1.22 g/ml fraction (20%) but had no effect on size and chemical composition of the particles. We conclude that PLTP and H-TGL promote the formation of small, pre-beta-like HDL particles from HDL2.
Atherosclerosis 1997 Aug
PMID:Transformation of high density lipoprotein 2 particles by hepatic lipase and phospholipid transfer protein. 925 11

We showed earlier that the apolipoprotein A-I Leu159-->Arg mutation (apoA-IFin) results in dominantly inherited hypoalphalipoproteinemia. In the present study we investigated the effect of the apoA-IFin mutation on lipoprotein profile, apoA-I kinetics, lecithin:cholesterol acyltransferase (LCAT) activation, and cholesterol efflux in vitro. Carriers (n = 9) of the apoA-IFin mutation exhibited several lipoprotein abnormalities. The serum HDL cholesterol level was diminished to 20% of normal, and nondenaturing gradient gel electrophoresis of HDL showed disappearance of particles at the 9.0- to 12-nm size range (HDL2-type) and the presence of small 7.8- to 8.9-nm (mostly HDL3-type) particles only. HDL3-type particles from both the mutation carriers and nonaffected family members were similarly converted to large, HDL2-type particles by phospholipid transfer protein in vitro. Studies on apoA-I kinetics in four affected subjects favored accelerated catabolism of apoA-I. Experiments with reconstituted proteoliposomes showed that the capacity of apoA-IFin protein to activate LCAT was reduced to 40% of that of the wild-type apoA-I. The impact of the apoA-IFin protein on cholesterol efflux was examined in vitro using [3H]cholesterol-loaded human fibroblasts and three different cholesterol acceptors: (1) total HDL, (2) total apoA-I combined with phospholipid, and (3) apoA-I isoform (apoA-IFin or wild-type apoA-I isoform 1) combined with phospholipid. ApoA-IFin did not impair phospholipid binding or cholesterol efflux from fibroblasts to any of the acceptors used. Only one of the nine apoA-IFin carriers appears to have evidence of clinically manifested atherosclerosis. In conclusion, although the apoA-IFin mutation does not alter the properties of apoA-I involved in promotion of cholesterol efflux, its ability to activate LCAT in vitro is defective. In vivo, apoA-IFin was found to be associated with several lipoprotein composition rearrangements and increased catabolism of apoA-I.
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PMID:Apolipoprotein A-IFIN (Leu159-->Arg) mutation affects lecithin cholesterol acyltransferase activation and subclass distribution of HDL but not cholesterol efflux from fibroblasts. 940 89

High density lipoproteins (HDL) encompass structurally and functionally heterogeneous particles. Two-dimensional nondenaturing polyacrylamide gradient gel electrophoresis (2D-PAGGE) and subsequent immunoblotting helps to differentiate quantitatively minor HDL-subclasses from the bulk of HDL, which contains apo A-I and has electrophoretic alpha-mobility. Pulse-chase experiments identified the quantitatively minor HDL subclasses prebeta1-LpA-I, gamma-LpE and LpA-IV as initial and fast acceptors of cell-derived cholesterol and alpha-migrating HDL (i.e. alpha-LpA-I) as a late and slow acceptor. In plasmas of patients with certain forms of familial HDL-deficiency such as apo A-I deficiency and Tangier disease, prebeta1-LpA-I, gamma-LpE and LpA-IV represent the only HDL particles and account for the significant residual cholesterol efflux capacity of these plasmas. These particles, however, also fulfill important roles in reverse cholesterol transport of normal plasma. Prebeta1-LpA-I, for example, is generated, during the interconversion of HDL by lipid transfer proteins. Thus, incubation of plasma with phospholipid transfer protein increases the concentration of prebeta1-LpA-I and in parallel increases the cholesterol efflux capacity of plasma indicating that lipid transfer proteins modulate cholesterol efflux by modification of HDL subclass composition. Apo E and gamma-LpE are of special interest for reverse cholesterol transport since macrophages can produce apo E.
Atherosclerosis 1998 Apr
PMID:High density lipoproteins and reverse cholesterol transport: lessons from mutations. 969 35

The aim of the present study was to investigate the high-density lipoprotein (HDL) structural characteristics and metabolism in hyperalphalipoproteinemic (HALP) patients (HDL-cholesterol [HDL-C], 92 +/- 14 mg/dL) with combined elevated low-density lipoprotein-cholesterol (LDL-C) levels (LDL-C, 181 +/- 33 mg/dL). Patients were subjected to a complete cardiovascular examination, including ultrasonographic investigation of carotid arteries. Two HALP profiles were identified according to the HDL2/HDL3 ratio. HALP profile A was characterized in 28 patients by increased HDL2/HDL3 ratio, HDL2b, and lipoprotein (Lp)A-I levels compared with normolipidemic subjects, and HALP profile B, including the 12 remaining patients, was characterized by a HDL2/HDL3 ratio within the normal range and by the increase of all HDL subclasses (HDL(2b,2a,3a,3b,3c)), LpA-I, and LpA-I:A-II levels. With regard to the exploration of carotid arteries, in HALP profile A, 20 patients were free from lesions and eight had only intimal wall thickening. In HALP profile B, only one patient was free from lesions, four had intimal wall thickening, and seven displayed plaques, but none had stenosis. Taking into account the number of patients with plaques within each group, HALP profile A was associated with a low prevalence of atherosclerotic lesions, whereas HALP profile B was less cardioprotective (odds ratio, 77.7 [95% confidence interval, 3.7 to 1,569.7]; P < .0001). For both HALP profiles, cholesteryl ester transfer protein (CETP) deficiency was discarded and activities of phospholipid transfer protein (PLTP) and lipoprotein lipase (LPL) were normal. However, hepatic lipase (HL) activity was significantly decreased in HALP profile A, but within the normal range for HALP profile B. In conclusion, an HALP profile A with a low prevalence of atherosclerosis was characterized by an increased HDL2/HDL3 ratio, HDL2b, and LpA-I levels associated with decreased HL activity.
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PMID:Hyperalphalipoproteinemia: characterization of a cardioprotective profile associating increased high-density lipoprotein2 levels and decreased hepatic lipase activity. 971 93

Low levels of high density lipoproteins (HDL) are associated with an increased risk for premature cardiovascular disease. The plasma phospholipid transfer protein (PLTP) is believed to play a critical role in lipoprotein metabolism and reverse cholesterol transport by remodeling HDL and facilitating the transport of lipid to the liver. Plasma contains two major HDL subclasses, those containing both apolipoproteins (apo) A-I and A-II, Lp(A-I, A-II), and those containing apo A-I but not A-II, Lp(A-I). To examine the potential relationships between PLTP and lipoproteins, plasma PLTP activity, lipoprotein lipids, HDL subclasses and plasma apolipoproteins were measured in 52 patients with documented cardiovascular disease and low HDL levels. Among the patients, plasma PLTP activity was highly correlated with the percentage of plasma apo A-I in Lp(A-I) (r=0.514, p < 0.001) and with the apo A-I, phospholipid and cholesterol concentration of Lp(A-I) (r=0.499, 0.478, 0.457, respectively, p < 0.001). Plasma PLTP activity was also significantly correlated with plasma apo A-I (r=0.413, p=0.002), HDL cholesterol (r=0.308, p=0.026), and HDL, and HDL3 cholesterol (r=0.284 and 0.276, respectively, p < 0.05), but no significant correlation was observed with Lp(A-I, A-I), plasma cholesterol, triglycerides, or apo B, very low density lipoprotein cholesterol or low density lipoprotein cholesterol. These associations support the hypothesis that PLTP modulates plasma levels of Lp(A-I) particles without significantly affecting the levels of Lp(A-I, A-II) particles.
Atherosclerosis 1999 Jan
PMID:Relationship between plasma phospholipid transfer protein activity and HDL subclasses among patients with low HDL and cardiovascular disease. 992 May 22


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