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)

Hyperlipidemia and hypertension, two major risk factors for accelerated atherosclerosis, undoubtedly contribute to the excessive cardiovascular morbidity and mortality experienced by renal transplant recipients. The present survey of posttransplant hyperlipidemia in 500 cyclosporine-treated patients documented a 37.6% incidence of hypercholesterolemia, which occurred within 6 months posttransplant in 82% of patients. An etiologic relation to corticosteroid therapy was suggested by the strong correlation between prednisone doses and cholesterol levels, by the reduced cholesterol levels in patients undergoing steroid withdrawal, and by the reduction in hypercholesterolemia to 13% by 3 years posttransplant when steroid doses were less than 10 mg daily. Hypertriglyceridemia, which was present in 14.7% of the patients, was more severe under CsA-prednisone compared with azathioprine-prednisone therapy. Hypertriglyceridemia, which occurred later in the posttransplant course than hypercholesterolemia, strongly correlated with an excessive percent relative weight and elevated serum creatinine but not with steroid or CsA doses. Increasing age, diabetes mellitus, beta-blockers and nephrotic syndrome contribute to posttransplant hyperlipidemia in the CsA-Pred era as they did in the azathioprine era of immunosuppression.
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PMID:Lipid abnormalities in cyclosporine-prednisone-treated renal transplant recipients. 266 33

An elevated serum cholesterol level is a well known major risk factor for developing atherosclerosis in general, and for coronary heart disease in particular. There are many lipid lowering agents currently available. We used gemfibrozil in twenty hyperlipidemic cases who failed to response to diet control for three months. They were thirteen males and seven females with their ages ranging from thirty to eighty-one year-old. They included ten diabetes, one nephrotic syndrome and nine pure hyperlipidemic patients. All cases received gemfibrozil 600mg twice daily for 4-12 weeks. Gemfibrozil caused an increase in HDL cholesterol. The reductions in serum level of total cholesterol, total cholesterol/HDL cholesterol, and triglyceride were found. Only one case developed mild gastrointestinal side effect. There was no other major side effects.
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PMID:[Gemfibrozil in the treatment of hyperlipidemia]. 276 68

Lecithin:cholesterol acyltransferase (LCAT) and lysolecithin acyltransferase (LAT) are two activities carried out by the same plasma enzyme, but require different apoprotein activators. The LCAT reaction takes place primarily on high density lipoproteins (HDL) and is activated by serum albumin, whereas LAT takes place on low density lipoproteins (LDL) and is inhibited by albumin. In nephrotic syndrome (NS), the levels of serum albumin are reduced, whereas the LDL levels are increased, and therefore, the ratio of LAT/LCAT activities should be increased. To test this hypothesis, we estimated the lipid levels and the two enzyme activities in experimental NS induced in rats by the injection of anti-Fx1A antibody (passive Heymann nephritis). As found in other nephrotic conditions, the plasma lipid levels rose progressively as the proteinuria increased and the serum albumin concentration declined. In addition, the ratio of LAT/LCAT activities increased by about fourfold after nine days of induction of nephritis. The LCAT activity correlated positively and the LAT activity negatively with serum albumin levels. The esterified cholesterol correlated positively with LCAT activity in normal rats but negatively in nephrotic animals, indicating that most of the cholesteryl esters in NS may be non-LCAT derived. The free cholesterol/lecithin ratio, a known risk factor for atherosclerosis, increased significantly in nephrotic rats. Furthermore, since the increase in the LAT activity produces more disaturated lecithins, another putative risk factor, the cumulative risk of coronary heart disease may be increased in long-term NS.
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PMID:Plasma lipids and acyltransferase activities in experimental nephrotic syndrome. 277 94

We investigated lipoprotein profiles in 24 children with normal renal function at different stages of the idiopathic nephrotic syndrome (NS). Four groups of patients were studied: (I) steriod-resistant NS with persistent proteinuria; (II) untreated steroid-sensitive NS during a relapse; (III) steroid-sensitive NS in remission induced by steroid-treatment; (IV) steroid-sensitive NS in long-term remission without therapy. Triglycerides (TG), cholesterol (CHOL), and phospholipids (PLP) were measured in plasma as well as in the lipoprotein fractions of very low (VLDL), intermediate (IDL), low (LDL) and high density (HDL). Apoproteins (Apo) AI, AII, B and C-apoproteins were measured in patients of groups I and IV. Results were compared to those obtained in 24 healthy control subjects. All patients with active NS (groups I-III) had significantly elevated CHOL levels. TG and CHOL in the VLDL, IDL, LDL, and CHOL in HDL2, but not HDL3 were inversely correlated with the serum albumin level. Patients with active NS had increased concentrations of TG and CHOL in lipoprotein fractions of lower density. Total and fractionated HDL-CHOL was not significantly different from control levels in any group. Patients in group I had significantly reduced Apo AI levels, whereas an increase of Apo AI and Apo AII in HDL3 and of most C-apoproteins in both HDL fractions was observed in patients of group IV. While changes in HDL apoprotein composition during long-term remission are of yet unknown clinical significance, our data indicate an increased risk of atherosclerosis only in those paediatric patients with persistent steroid-resistant NS.
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PMID:Lipoprotein profiles at different stages of the nephrotic syndrome. 339 Dec 17

The hyperlipidemia of the nephrotic syndrome is often associated with elevated total and low-density lipoprotein (LDL) cholesterol levels and low or normal high-density lipoprotein (HDL) cholesterol levels. This pattern of hyperlipidemia has been associated with an increased risk of accelerated atherosclerosis in other populations. Despite extensive studies of diet and drug therapy in other populations, few such therapeutic studies exist in patients with the nephrotic syndrome. To investigate the effect of diet and lipid-lowering drugs on the lipoprotein-lipid profile of patients with unremitting nephrotic syndrome and marked hyperlipidemia, we conducted a controlled trial using two such drugs: colestipol and probucol. Colestipol lowered the mean total fasting plasma cholesterol of seven patients from 397 +/- 27 to 317 +/- 37 mg/dL, a 20.2% decrease, and lowered the LDL cholesterol from 398 +/- 28 to 203 +/- 18 mg/dL, a 31.9% decrease. It did not affect the HDL cholesterol level, and thus lowered the LDL-to-HDL cholesterol ratio. Probucol lowered the mean total cholesterol from 439 +/- 72 to 339 +/- 60 mg/dL, a 22.6% decrease, and the LDL cholesterol from 282 +/- 43 to 215 +/- 26 mg/dL, a 23.8% decrease. Although the HDL cholesterol was lowered from 49 +/- 9 to 43 +/- 7 mg/dL by probucol, a 12.2% decrease, the LDL-to-HDL cholesterol ratio still declined. Both drugs were well tolerated and proved safe in this short-term trial. Antihyperlipidemic therapy may well be indicated in certain patients with unremitting nephrotic syndrome.
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PMID:Treatment of the hyperlipidemia of the nephrotic syndrome: a controlled trial. 354 20

Plasma lipoprotein profiles were quantitated in 9 patients with the nephrotic syndrome. Six subjects were studied both during an active proteinuric phase and during a remission phase without proteinuria. During the proteinuric phase, the plasma triglyceride, cholesterol and apo B levels were markedly increased, whereas the HDL cholesterol, apo A-I, and apo A-II concentrations were normal. Analysis of the distribution and composition of the lipoprotein subclasses, separated by isopycnic ultracentrifugation, showed typical patterns characterized by: (1) elevated apo B-rich VLDL and LDL fractions, (2) the presence of a denser LDL subfraction, floating at d 1.053 g/ml, which contained about 35% of LDL cholesterol and apo B and (3) a redistribution among HDL subclasses. The HDL2b (d 1.063-1.100 g/ml) fraction was markedly decreased, while the HDL2a + 3a (d 1.100-1.150 g/ml) and HDL3b + 3c (d 1.150-1.210 g/ml) subclasses were moderately elevated. The decreased cholesterol and apo A-I contents of HDL2b therefore counterbalanced their increase in HDL2a + 3a and HDL3b + 3c, resulting in normal plasma HDL cholesterol and apo A-I concentrations. When reinvestigated during a remission phase without proteinuria, the nephrotic patient's overall lipoprotein distribution and composition were similar to those in healthy controls. The combination of several factors such as the presence of elevated apo B-rich VLDL, IDL and LDL, together with decreased HDL2 cholesterol and HDL2 apo A-I suggests that nephrotic patients are at increased risk for atherosclerosis.
Atherosclerosis 1985 Feb
PMID:Lipoprotein distribution and composition in the human nephrotic syndrome. 398 19

We investigated the severity and duration of hyperlipidemia in 59 nephrotic children during relapse and remission. Serum total cholesterol and triglyceride values were greater than or equal to 95th percentile for age and sex in all patients with minimal change nephrotic syndrome in relapse and in patients with non-MCNS and persistent proteinuria. Most of these patients also had a significant elevation of low- and very-low-density lipoproteins. A significant number of children with MCNS during prolonged remission had elevated serum concentrations of total cholesterol (46%), triglycerides (42%), LDL (29%), and VLDL (40%). Persistence and severity of lipid changes correlated well with duration of disease and frequency of relapses. Significantly decreased HDL and HDL/LDL were found in patients with non-MCNS and persistent proteinuria. Our results suggest that nephrotic children may have prolonged periods of hyperlipidemia even after clinical remission. In addition, some of these children with significantly decreased HDL/LDL may be at increased risk of developing premature atherosclerosis.
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PMID:Persistence of serum lipid abnormalities in children with idiopathic nephrotic syndrome. 669 Jun 76

Patients with analgesic nephropathy are reported to have a higher risk of atherosclerosis. One possible reason for this is a high incidence of hyperlipaemia in patients with analgesic nephropathy. In a retrospective study, serum cholesterol and serum triglyceride concentrations of patients with analgesic nephropathy and moderately restricted renal function were significantly higher compared to a control group with other renal diseases of similar age and degree of renal insufficiency. Hyperlipaemia in analgesic nephropathy is not explained by end-stage renal failure on one side or protein loss as in nephrotic syndrome on the other side. Some possible mechanisms for hyperlipaemia in analgesic nephropathy are discussed.
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PMID:Hypercholesterolaemia and hypertriglyceridaemia in patients with analgesic nephropathy. 741 66

Lipoprotein (a) is a relatively new independent risk factor of early atherosclerosis with atherogenic and thrombogenic properties. From the structural aspect it resembles LDL-lipoprotein and differs from the latter by the presence of another glycoprotein-apolipoprotein (a). Due to the great similarity of apolipoprotein (a) and plasminogen, lipoprotein (a) is bound to plasminogen receptors on the fibrin surface (fibrinogen) and thus prevents the cumulation and activation of local fibrinolysis. Its levels are under strict genetic control and are very little influenced by external factors and available hypolipidaemic treatment. There is a great interindividual variability of lipoprotein(a) concentrations which is due above all to the structural variability of apolipoprotein (a). At present at least 34 isoforms of apolipoprotein(a) were described which differ as to the size of the molecule. This great structural variability has an impact not only on the function and pathogenicity of lipoprotein (a) but also on methods of its assessment. High lipoprotein(a) concentrations are found in subjects with early clinical manifestations of atherosclerosis, in nephrotic syndrome, in chronic renal insufficiency, in haemodialyzed patients and other diseases. They rise in women after the menopause and are favourably influenced by hormonal substitution therapy. There is a number of immunochemical methods used for its estimation which are very well reproducible within the same laboratory. The high interlaboratory coefficients of variation indicate, however, that unification of lipoprotein(a) analyses is urgent.
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PMID:[Lipoprotein (a): a genetic risk factor with atherogenic and thrombogenic properties]. 748 54

Hyperlipidemia of nephrotic origin could potentially cause glomerular injury as well as increase the risk of atherosclerosis. The precise interaction of human lipoproteins abnormal in lipid and protein composition, with lipoprotein receptors has not been clearly defined. This study examines receptor-mediated uptake and intracellular cholesterol metabolism of apolipoprotein (apo)B,E containing intermediate-density lipoprotein (IDL) and apoB-100 containing low-density lipoprotein (LDL), isolated from patients with the nephrotic syndrome (N = 6), in human glomerular mesangial and HepG2 cells. In the patients, serum IDL and LDL cholesterol levels were significantly increased as compared with those of healthy subjects. The IDL of nephrotic patients contained 80% more cholesterol than the IDL of healthy controls. No differences in lipid/protein composition were found in the LDL density range. Therefore, nephrotic and control LDL showed identical affinities for receptor-mediated uptake. In contrast, the IDL of nephrotic patients was taken up by mesangial cells and HepG2 with higher affinity than the LDL. Intracellular sterol synthesis was suppressed more effectively and cholesterol esterification rate was enhanced 2.2-fold by nephrotic IDL as compared with control IDL. These data indicate that hypercholesterolemia of nephrotic origin cannot be explained by reduced ligand binding for LDL. ApoE-containing IDL of patients with the nephrotic syndrome were avidly taken up by glomerular mesangial cells and could therefore play the predominant role in the development of glomerulosclerosis and atherosclerosis associated with this disorder.
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PMID:Preferential uptake of intermediate-density lipoproteins from nephrotic patients by human mesangial and liver cells. 784 47


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