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)

Human xanthomas derived from four subjects with familial hypercholesterolemia (3 homozygotes and 1 heterozygote) were studied by immunohistochemical methods to determine the presence and distribution of lipoproteins, which have been implicated in the pathogenesis of atherosclerosis. Oxidatively modified low-density lipoprotein (OxLDL) epitopes detected with anti-OxLDL monoclonal antibodies, appeared to have a similar distribution in xanthomata to that of macrophages, detected by a cell-specific monoclonal antibody. Double antibody labeling with both an anti-macrophage antibody and an anti-OxLDL antibody demonstrated that OxLDL epitopes are associated with macrophages and occurred intracellularly. Low-density lipoprotein (LDL) epitopes were detected extracellularly, with a distribution that was different from that of OxLDL. In addition, apo(a) epitopes detected by an apo(a) specific monoclonal antibody, had a distribution similar to that of LDL in the dermis and subcutaneous tissues. The observed epitope distribution of LDL, OxLDL, or apo(a) was the same regardless of the method of treatment of the patients from whom the xanthomas were obtained (probucol, simvastatin, LDL apheresis). These findings suggest that OxLDL is likely to play a pathogenetic role in the lipid accumulation by macrophages in xanthomas, and suggest that Lp(a) also may play a role in their pathogenesis.
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PMID:Immunohistochemical distribution of lipoprotein epitopes in xanthomata from patients with familial hypercholesterolemia. 137 98

It has been shown that blacks have considerably higher concentrations than whites of lipoprotein(a) (Lp(a)), which has been identified as an independent risk factor for coronary heart disease, vein graft restenosis, and cerebrovascular disease. Smaller differences in Lp(a) concentrations have been noted between males and females. To examine whether gender and race differences are already detectable at birth, we examined Lp(a) concentrations in cord blood samples of 109 black (49 male and 60 female) and 123 white (67 male and 56 female) newborns. Maternal age, gestational age, fetal maturity indicators, weight, height and head circumference were analyzed as covariates. For race and sex combined, the mean Lp(a) concentration was 4.0 mg/dl (S.D. of 3.94 mg/dl), approximately 5-fold lower than that observed in adults. No statistically significant differences were found between race or gender groups. The cross-sectional examination of serum Lp(a) concentrations of 221 infants, children and adults showed a gradual increase in Lp(a) concentrations from birth to adult values by the second year of life. We conclude that the system responsible for the production and control of Lp(a) concentration is not yet mature--or has not yet been challenged--at birth.
Atherosclerosis 1992 Feb
PMID:Lipoprotein(a) at birth, in blacks and whites. 138 53

The plasma lipoprotein(a) (Lp(a)) concentration and apolipoprotein(a) (apo(a)) phenotype were determined in the members of two families affected with familial defective apo B100 (FDB), resulting from the Arg3500----Gln mutation in apo B that disrupts binding to LDL receptors. Eleven different phenotypic species of apo A were identified, five of which were present in both families. Although there was a general increase in Lp(a) concentration as the size of the predominant apo(a) component decreased, there was considerable variability and in three clear instances the concentration of an inherited phenotypic species was atypically low. In five cases where a direct comparison could be made, the plasma Lp(a) concentration was significantly higher in heterozygous FDB subjects than in their non-FDB siblings or close relatives with the same phenotype. However, in vitro competition studies using purified Lp(a) that had been reduced with dithiothreitol to remove the apo(a) component, indicated that the Lp(a) from FDB heterozygotes contained a smaller proportion of defective particles than their LDL. Lp(a) particles containing normal and binding-defective apo B were present at approximately the same concentration, suggesting that the increase in Lp(a) concentration observed in FDB subjects could not be explained by the inability of the particles containing the defective apo B100 to be cleared through LDL-receptor mediated processes.
Atherosclerosis 1992 Feb
PMID:Lipoprotein(a) in subjects with familial defective apolipoprotein B100. 138 54

Lp(a) is an LDL-like lipoprotein which contains an additional apolipoprotein called apo(a). Apo(a) exhibits a significant size polymorphism and its size is inversely correlated with plasma Lp(a) levels. We investigated the distribution of different apo(a) isoproteins in lipoprotein density fractions. Fasting plasma samples were subjected to non-equilibrium density gradient ultracentrifugation. After SDS-PAGE and anti-apo(a) immunoblotting, apo(a) concentrations in individual density fractions were evaluated by densitometry. In series I, analysis of selected density fractions from 35 coronary heart disease (CHD) patients demonstrated that although most of the apo(a) was present in the Lp(a) density range, apo(a) was consistently found in both the VLDL and IDL fractions as well. In series II, density fractions from 9 normolipidemic subjects with 6 different apo(a) isoproteins were evaluated. A strong association between the size of the apo(a) isoprotein and the density of the associated Lp(a) particle was established (r = 0.976, P less than 0.001). Lp(a) densities ranged from 1.057 g/ml for the B isoprotein to 1.09 g/ml for the S5 isoprotein. Overall, 75% of the total apo(a) was detected in the Lp(a) density range (d = 1.05-1.12 g/ml), with 9% and 10% in the LDL (d = 1.019-1.05 g/ml) and HDL (d = 1.12-1.21 g/ml) fractions, respectively. VLDL contained an average of 4% of the total apo(a) in fasting normolipidemic plasma. Two hypertriglyceridemic subjects had substantially greater amounts of apo(a) in the fasting triglyceride-rich fraction. The results of this study indicate that the size of the apo(a) isoprotein strongly influences the density of its associated Lp(a) particle and that apo(a) is consistently found in the triglyceride-rich lipoproteins of fasting plasma.
Atherosclerosis 1992 Jun
PMID:Correlation of apolipoprotein(a) isoproteins with Lp(a) density and distribution in fasting plasma. 138 58

Thirty-three consecutive unselected patients with primary hypercholesterolemia received niceritrol 1.5 g daily for 12 weeks, with the effect of administering divided dose (twice daily (b.i.d.) and three times daily (t.i.d.)) evaluated. The serum concentrations of lipoprotein(a) (Lp(a)), lipids, the major apolipoproteins (apo), cholesteryl ester transfer activity and fibrinogen were determined before and after treatment. The b.i.d. and t.i.d. regimens each significantly reduced the serum levels of total cholesterol and triglyceride. The mean changes in serum lipids and lipoproteins did not differ significantly between the two groups. After 12 weeks of treatment, there was a significant decrease in total plasma cholesterol, triglyceride, low density lipoprotein cholesterol, apo A-II, apo B and fibrinogen and an increase in the high density lipoprotein cholesterol levels. Although the serum level of Lp(a) did not change in every patient, niceritrol significantly reduced the serum Lp(a) level in those with an initially high level of Lp(a) (greater than or equal to 20 mg/dl).
Atherosclerosis 1992 Jun
PMID:Effects of niceritrol on levels of serum lipids, lipoprotein(a), and fibrinogen in patients with primary hypercholesterolemia. 138 59

Lipoprotein(a) is an independent risk factor for cardiovascular disease. Lipoprotein(a) levels were measured in 196 patients (103 Male [M]: 93 Female [F]) with chronic renal diseases and in 116 controls. Median levels of Lipoprotein(a) [Lp(a)] were found to be significantly elevated in patients with untreated chronic renal disease (285,285 mg/L; M,F; range 30-1675 mg/L) and in those treated with continuous ambulatory peritoneal dialysis (320, 603; M,F; range 50-1450) compared with controls (70,51; M,F; range 1-750; p less than 0.01 Males, p less than 0.001 Females). Lp(a) levels in patients treated by haemodialysis (133,35; M,F; range 5-685) and renal transplantation (100,95; M,F; range 10-1700) were not significantly different from controls. Lipoprotein(a) levels correlated inversely with serum albumin in the combined dialysis group (r = -0.34, p less than 0.001), and with urinary protein loss in the combined transplant and chronic renal diseases groups (r = 0.29, p less than 0.01). This correlation of Lp(a) with protein metabolism suggests a similarity with changes in other apolipoprotein-B containing lipoproteins in nephrosis. These findings may be relevant to the increased risk of atherosclerosis in patients with chronic renal disease and to their optimum mode of renal replacement therapy.
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PMID:Lipoprotein(a) levels in chronic renal disease states, dialysis and transplantation. 138 27

A screening study was performed on 106 children with familial risk for coronary heart disease (CHD) and on matched controls. The two groups differed in several parameters. Children of CHD patients exhibited significantly elevated levels of Lp(a) and total cholesterol, reduced HDL apo A1 and apo A2 and increased values of serum hexuronic acid. These results support the concept that genetic and familial factors contribute to the risk of atherosclerosis.
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PMID:Lp(a) and the risk of coronary heart disease. 138 93

Blood monocytes or intimal smooth muscle cells from normal aorta were incubated with low density lipoprotein (LDL) from patients with coronary atherosclerosis, or with LDL from diabetic patients, or with lipoprotein(a) (Lp(a)). In each case there was a 2- to 4-fold rise in the intracellular cholesteryl ester content. LDL from healthy subjects failed to induce intracellular lipid accumulation in these cells. LDL from patients with coronary atherosclerosis, LDL from diabetic patients, and Lp(a) form aggregates under cell culture conditions. The ability of these lipoproteins to increase the cholesteryl ester content of cultured cells is directly correlated to the degree of lipoprotein aggregation. When aggregates were removed from the lipoprotein preparations by filtration, the latter became less effective in promoting intracellular lipid accumulation. Incubation of cells with lipoprotein aggregates, isolated by gel filtration, induced a 3- to 5-fold elevation of the cellular cholesteryl ester content. These results suggest that LDL from atherosclerotic patients, or LDL from diabetic patients, or Lp(a) have a tendency to form aggregates and that these aggregates are avidly taken up by intimal smooth muscle cells followed by lipid accumulation. This aggregation tendency may play a role in atherogenesis.
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PMID:Three types of naturally occurring modified lipoproteins induce intracellular lipid accumulation in human aortic intimal cells--the role of lipoprotein aggregation. 138 57

The aims of this study were to evaluate plasma lipid, apoprotein and Lp(a) levels in patients with severe coronary atherosclerosis undergoing aorto-coronary bypass surgery (BP) and to relate these parameters to the involvement of one or more vessels. Seventy-seven male patients and 77 cardiovascular disease-free controls, matched for sex, age and body weight were studied. Higher triglyceride and apo B levels with lower HDL-cholesterol and apo A-I levels were found in BP patients in comparison with the controls. Lp(a) levels were slightly, but not significantly, increased. Moreover BP patients presented a significantly higher prevalence of HDL-cholesterol levels below 35 mg dl-1 (49.3% vs 22.1%) and Lp(a) levels above 70 mg dl-1 (10.4% vs 1.3%) than the controls. When patients were divided according to the number of coronary vessels involved (one, two or three), no significant difference was found, with a trend to increase in Lp(a) mean levels and in prevalence of Lp(a) levels above 30 and 70 mg dl-1 in more severely diseased patients. These results suggest that patients with severe coronary artery disease undergoing aorto-coronary bypass surgery show low HDL-cholesterol levels with high triglyceride levels. Moreover Lp(a) levels above 70 mg dl-1 are highly associated with severe coronary vessel stenosis.
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PMID:Lp(a) levels in patients undergoing aorto-coronary bypass surgery. 139 16

Lipoprotein(a) [Lp(a)] is recognized as an independent risk factor for atherosclerosis. Lp(a) consists of a LDL-like moiety with an additional glycoprotein, apo(a), linked to apolipoprotein B-100. Apo(a) has a high homology with plasminogen (Pg). In vivo, Pg is activated on a fibrin surface by tissue Pg activator (tPA). We prepared Lp(a) from plasma by sequential ultracentrifugation followed by lysine-sepharose affinity chromatography. We found that a changing (donor dependent) fraction of the Lp(a) did not bind to lysine-sepharose. This fraction, designated Lp(a)lys-, was further purified using gel filtration. Bound Lp(a) [Lp(a)lys+] was eluted with 0.2 M EACA. Apo(a) isoforms in both fractions were identical. In contrast Lp(a)lys+ inhibited Pg activation by tPA in vitro (IC50% 20 mg/l), whereas Lp(a)lys- did not. In addition Lp(a)lys- did not bind to CNBr-digested fibrinogen whereas Lp(a)lys+ did (Kd, app = 0.2 nM). Therefore we conclude that a changing donor dependent fraction of human plasma Lp(a) does not inhibit Pg activation in vitro and does not bind to CNBr-digested fibrinogen.
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PMID:Lysine-binding heterogeneity of Lp(a): consequences for fibrin binding and inhibition of plasminogen activation. 141 65


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