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)

Absent hepatic lipase (HL) activity results in dyslipidemia and premature atherosclerosis. DNA sequencing of the HL gene from subjects with heritable HL deficiency identified a new C to T substitution within exon 8 that in the mature enzyme caused a threonine to methionine change at position 383 (T383M). With a rapid DNA detection method we observed that all 6 individuals with complete HL deficiency from 2 families had the T383M mutation. None of 50 random unrelated unaffected subjects had this mutation. We propose that T383M is specific to families with heritable HL deficiency. Furthermore, structural variation at the HL gene, possibly in combination with other factors, appears to be etiologic in HL deficiency.
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PMID:A hepatic lipase gene mutation associated with heritable lipolytic deficiency. 167 86

Small high density lipoproteins (HDL) with pre-beta electrophoretic mobility (pre-beta HDL) have recently been shown to be the primary acceptor of cholesterol from cultured cells. We studied the metabolism of these particles by incubating serum at 37 degrees C in the presence and absence of active lecithin: cholesterol acyltransferase (LCAT). We found that the serum pre-beta HDL concentration decreased in the presence of LCAT, but when LCAT was inhibited the concentration remained constant, or increased, depending on the method of inhibition. This suggests that pre-beta HDL are a substrate for LCAT. We also found a significant negative correlation between levels of LCAT activity and pre-beta HDL in 28 fasting healthy subjects, this provides evidence that the activity of LCAT regulates, at least in part the concentration of these particles in vivo. During the early phase of incubation there was a more rapid decrease in pre-beta HDL concentration which was greater in the post-prandial than fasting state. When we infused a triglyceride emulsion into 6 subjects or added this to serum in vitro we observed an immediate fall in pre-beta HDL concentration. These findings suggest that pre-beta HDL interact with triglyceride rich particles. We investigated the origin of pre-beta HDL from blood lipoproteins during their lipolysis, in vivo and in vitro and found that they were produced from both triglyceride-rich and high-density lipoproteins. Formation from triglyceride-rich lipoproteins was evident by the rise in pre-beta HDL concentration during heparin-induced lipolysis when fasting and post-prandially. The rise was greater post-prandially and particularly marked in 4 hypertriglyceridaemic patients following a fat load. Generation from alpha-HDL was evident when we prolonged the action of the heparin-released lipases by incubation of post-heparin sera at 37 degrees C. Continued formation of pre-beta HDL occurred at an equal rate in the fasting and post-prandial samples suggesting release by lipolysis of alpha-HDL. This was supported by the action of lipases on serum and isolated HDL in vitro, where triglyceride lipase rather than phospholipase activity appeared more effective at releasing pre-beta HDL. These findings suggest binding and release of pre-beta HDL by triglyceride-rich lipoproteins depending on the prandial state and production from alpha-HDL through the action of lipases.
Atherosclerosis 1991 Jul
PMID:An investigation of the role of lecithin:cholesterol acyltransferase and triglyceride-rich lipoproteins in the metabolism of pre-beta high density lipoproteins. 177 70

The relations between postheparin plasma lipase activities and concentrations of lipoproteins, in particular plasma high density lipoprotein (HDL) subclasses determined by gradient gel electrophoresis, were examined in 39 men who had survived a first myocardial infarction before the age of 45 years and in 20 age-matched control men. Reduced lipoprotein lipase (LPL) and hepatic lipase (HL) activities were found in the patients due to low LPL activity in patients with hypertriglyceridaemia, and low HL activity in those with a normal lipoprotein pattern or hypercholesterolaemia. Considerably lower plasma HDL2b and HDL2a protein concentrations and higher plasma HDL3b and HDL3c protein levels were found in the patients compared with the healthy control subjects. The subgroup of patients with hypertriglyceridaemia accounted for the major proportion of the case control differences for the HDL subspecies. However, significantly lower HDL2b and HDL2a concentrations were seen also among the normotriglyceridaemic patients. Analysis of the correlations between concentrations of HDL subclasses and lipase activities revealed positive associations between LPL and HDL2b and negative associations between HL and HDL2b. For LPL, this relationship was confined to hypertriglyceridaemic and for HL to normotriglyceridaemic subjects. HL was indicated to be positively connected with HDL3b levels, irrespective of lipoprotein pattern, whereas LPL seemed to be unassociated with HDL3b. It is concluded that low LPL and HL activities partly account for the change in HDL subclass distribution observed in patients with myocardial infarction at a young age.
Atherosclerosis 1991 Feb
PMID:The association of lipoprotein and hepatic lipase activities with high density lipoprotein subclass levels in men with myocardial infarction at a young age. 187 6

In a kindred with three hyperlipidemic subjects who had premature atherosclerosis and complete deficiency of hepatic lipase activity, we had previously identified a novel structural hepatic lipase gene variant. We now report the identification of three more hepatic lipase gene mutations in this family and demonstrate that compound heterozygosity for two hepatic lipase mutations (designated S267F and T383M) underlies hepatic lipase deficiency.
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PMID:Compound heterozygosity for mutant hepatic lipase in familial hepatic lipase deficiency. 188 93

Low HDL-cholesterol (HDL-C) levels may elevate atherosclerosis risk, and often associate with hypertriglyceridemia (HTG); however, the metabolic causes of low HDL-C levels with or without HTG are poorly understood. We studied the turnover of radioiodinated HDL apolipoproteins, apo A-I and apo A-II, in 15 human subjects with low HDL-C, six with normal plasma TG levels (group 1) and nine with high TG (group 2), and compared them to 13 control subjects with normal HDL-C and TG levels (group 3). The fractional catabolic rate (FCR) was equally elevated in groups 1 and 2 vs. group 3 for both apo A-I (0.313 +/- 0.052 and 0.323 +/- 0.063 vs. 0.245 +/- 0.043 pools/d, P = 0.003) and apo A-II (0.213 +/- 0.036 and 0.239 +/- 0.037 vs. 0.185 +/- 0.031 pools/d, P = 0.006). Thus, high FCR characterized low HDL-C regardless of the presence or absence of HTG. In contrast, transport rate (TR) of apo A-I did not differ significantly among the groups and the apo A-II TR differed only between groups 2 and 3 (2.15 +/- 0.57, 2.50 +/- 0.39, and 1.83 +/- 0.48 mg/kg per d for groups 1 to 3, respectively, P = 0.016). Several HDL-related factors were similar in groups 1 and 2 but differed in group 3, as with FCR, including the ratio of lipoprotein lipase to hepatic lipase activity (LPL/HL) in post-heparin plasma, the ratio of the HDL-C to apo A-I plus apo A-II levels, and the percent of tracer in the d greater than 1.21 fraction. In linear regression analysis HDL-C levels correlated inversely with the FCR of apo A-I and apo A-II (r = -0.74, P less than 0.0001 for both). Major correlates of FCR were HDL-C/apo A-I + apo A-II, LPL/HL, and plasma TG levels. We hypothesize that lipase activity and plasma TG affect HDL composition which modulates FCR, which in turn regulates HDL-C. Thus, HTG is only one of several factors which may contribute to elevated FCR and low HDL-C. Given the relationship of altered HDL composition with high FCR and low HDL-C levels, factors affecting HDL composition may increase atherosclerosis susceptibility.
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PMID:Increased apo A-I and apo A-II fractional catabolic rate in patients with low high density lipoprotein-cholesterol levels with or without hypertriglyceridemia. 189 29

Serum low-density lipoprotein (LDL) concentration is a major determinant of susceptibility to the development of atherosclerosis. A major component of the protein moiety of LDL and its precursor very-low-density lipoprotein is apolipoprotein B (apo B). The human hepatoma cell line, Hep G2, was used as a model for the investigation of mechanisms which control hepatic secretion of the apo B and lipid components of lipoproteins. Using a sensitive immunoradiometric assay for apo B developed in this laboratory, we showed that bovine serum albumin inhibited and glucose, and fatty acids enhanced the rate of accumulation of apo B in the culture medium of Hep G2 cells. However, these substances did not necessarily affect LDL lipids in the same way as apo B. This finding appeared to be due to Hep G2 cells expressing lipase activities which led to triacylglycerol and phospholipid hydrolysis and lipid reuptake. Reuptake of apo B also occurred, but its rate of accumulation in the culture medium suggested it was a closer reflection of its true secretory rate.
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PMID:Lipoprotein secretion by the human hepatoma cell line Hep G2: differential rates of accumulation of apolipoprotein B and lipoprotein lipids in tissue culture media in response to albumin, glucose and oleate. 195 47

Lipoprotein lipase is the rate determining enzyme for the removal of triglyceride rich lipoproteins from the blood stream. We examined whether genetic variation at the lipoprotein lipase gene locus is related to the occurrence of premature coronary artery disease. Two restriction fragment length polymorphisms, revealed by the enzymes HindIII and PvuII, demonstrated alleles designated H1 (17.5 kb), H2 (8.7 kb), P1 (7.0 kb), P2 (4.4 kb and 2.5 kb) respectively. These were studied in 70 Caucasian subjects with severe coronary atherosclerosis in comparison with 122 Caucasian healthy controls. The allelic frequencies for cases and controls were respectively: H2 0.770, 0.579 (P less than 0.001); P2 0.575, 0.554 (P NS). The allelic frequencies of the HindIII and BglII polymorphic sites at the hepatic lipase gene locus were also studied in the same groups of subjects. These showed no differences between cases and controls. We conclude that DNA variation at or adjacent to the lipoprotein lipase gene may contain genetic determinants for the occurrence of premature coronary artery disease.
Atherosclerosis 1990 Nov
PMID:Lipoprotein and hepatic lipase gene variants in coronary atherosclerosis. 198 Aug 16

A delayed clearance of postprandial lipoproteins from the plasma may play a role in the etiology of premature coronary atherosclerosis. To address this hypothesis, we studied chylomicron (remnant) metabolism in two groups of 20 selected normolipidemic men aged 35-65 years, a group of coronary artery disease (CAD) patients, and a matched control group with documented minimal coronary atherosclerosis. Subjects received an oral fat load supplemented with cholesterol and retinyl palmitate. Plasma samples obtained during the next 24-hour period were analyzed for total as well as d less than 1.019 g/ml and d greater than 1.019 g/ml triacylglycerol, cholesterol, and retinyl ester concentrations. Although both groups of patients responded identically in terms of the appearance of gut-derived lipids in the plasma, CAD patients showed a marked delay in the clearance of retinyl esters as well as in the normalization of plasma triacylglycerol concentrations. Postheparin plasma hepatic lipase activity was significantly lower in the CAD group. Apolipoprotein E phenotype measurements did not reveal marked differences in frequency between both groups. The frequency distribution was not unusual in comparison with the normal Dutch population. The magnitude of the postprandial responses of triacylglycerol and retinyl esters was correlated positively with the fasting levels of plasma triacylglycerol and negatively with high density lipoprotein subfraction 2 cholesterol concentrations. These data indicate that the clearance of postprandial lipoproteins in normolipidemic CAD patients as selected in the present study is delayed as compared with that of controls without coronary atherosclerosis and suggest that postprandial lipoproteins may play a role in the etiology of their disease.
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PMID:Postprandial lipoprotein metabolism in normolipidemic men with and without coronary artery disease. 202 3

Hepatic, heparin-releaseable lipase is a multifunctional enzyme that may act on all lipoprotein classes present in plasma from fasted subjects. Recent evidence suggests that the enzyme also plays a role in the metabolism of chylomicronremnants. Its activity is impaired in normolipidemic patients with coronary heart disease, which also have a delayed removal of chylomicronremnants from plasma. Therefore hepatic lipase, in addition to lipoprotein lipase, plays an important role in postprandial lipoprotein metabolism. The activity levels of lecithin: cholesterol acyltransferase (LCAT) and cholesterylester transfer protein (CETP) are virtually unchanged after the ingestion of an oral fat load by normolipidemic subjects. However, the net mass transfer of cholesterylesters out of HDL into apo B-containing lipoproteins (chylomicronremnants, VLDL/IDL/LDL) is strongly increased. All triglyceride-rich lipoprotein fractions accumulate postprandially and, as a result of CETP action, become enriched in cholesterylesters. Defects in hepatic remnant removal may result in influx of remnants into the arterial wall. In patients with hyperlipidemia (and increased risk for atherosclerosis) the CETP-mediated formation of cholesterylester-rich remnants may operate, not only during the postprandial phase, but continuously.
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PMID:[Role of hepatic lipases, cholesterol ester transfer proteins and LCAT in the postprandial phase]. 208 75

The effect of chronic renal failure on the lipid and apolipoprotein concentrations of plasma, very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), low density lipoproteins (LDL) and high density lipoproteins (HDL) was studied in an experimental uremic rat model. Control rats were sham-operated and were divided into adlibitum-fed and pair-fed groups. The rats were studied (after an overnight fast) 32 days after the onset of uremia. The uremic rats had a 4-fold increase in plasma urea nitrogen and creatinine. The pair-fed and ad-lib-fed controls had similar levels of plasma urea nitrogen and lipid profiles. In the uremic rats, plasma triglyceride (TG) levels were increased 3.8-fold due to increased TG in the VLDL, IDL and HDL fractions. Their 2-3-fold increase in plasma free cholesterol (FC), esterified cholesterol (EC) and phospholipids (PL) were due to FC, EC and PL increases in VLDL, IDL, LDL and HDL. Their increase in plasma apo B (x 2.4) and apo E (x 1.5) were due to increases in VLDL, IDL and LDL. Their plasma apo A-I increased 2.4 fold due to increases in the LDL and HDL fractions. Uremic rats also had increases in the FC/PL molar ratio in VLDL, IDL and LDL. In their LDL, the apo B/total cholesterol (TC), apo B/PL and apo B/apo E molar ratios were decreased. In their HDL, the apo E/TC and apo E/PL molar ratios were decreased and the apo A-I/apo E molar ratio was increased. In conclusion, chronic uremia causes both quantitative changes in the levels and qualitative changes in the composition of the plasma lipoprotein particles. These results are compatible with the decreased hepatic lipase activities and impairment of remnant clearance observed in human chronic renal failure.
Atherosclerosis 1990 Dec
PMID:Changes in the composition of plasma lipoproteins in the chronic uremic rat. 210 77


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