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)

Dyslipidemia is a major risk factor for atherosclerosis in adults and children. This study investigated the levels of lipoproteins in a northern Italian pediatric population, in relation to nutritional and familial factors. We studied 650 children on the basis of a 3-day dietary record; 361 of these children had their lipid levels [total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglycerides] measured by a dry, multilayer method and apoprotein A-I and B by an immunonephelometric method. Familial history of cardiovascular disease and dyslipidemia was recorded. Anthropometric variables were taken for each child. Mean TC and low-density lipoprotein cholesterol (LDL-C) were high compared with southern Italian data, but similar to those of other Western countries. Family history of cardiovascular disease could not identify children with higher levels of atherogenic lipoprotein. Nutritional factors affected lipoprotein levels. The most important finding was a higher TC/HDL-C ratio in the lower quartile of polyunsaturated fatty acid intake. Obese children had higher levels of ApoB, triglycerides, TC and LDL-C, and lower levels of HDL-C; figures were higher for obese boys than for obese girls. Our study confirms a high prevalence of elevated levels of atherogenic lipoproteins among the northern Italian pediatric population and an association with nutritional factors and weight.
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PMID:Cholesterol and lipoprotein levels in Milanese children: relation to nutritional and familial factors. 161 95

In recent years, LDL-apheresis has emerged to be an efficient treatment of hyperlipidemia in patients who do not respond sufficiently to diet and lipid lowering drugs. A survey of LDL lowering extracorporeal procedures is presented. Among them, to date 5 procedures have been used clinically on a routine basis: unselective plasma exchange, semi-selective double filtration (including its modifications like thermofiltration and predilution/backflush) and three highly selective LDL-apheresis systems: LDL-adsorption on dextran sulfate coated cellulose beads or anti-apoprotein B-linked sepharose and heparin induced extracorporeal LDL and fibrinogen precipitation (the so-called HELP system). Advantages, limitations and special indications of these commercially available systems are discussed. If atherosclerosis can really be made regress by drastic reduction of elevated serum cholesterol levels as indicated by recent publications, lipid apheresis will no doubt play a major role in attaining this goal.
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PMID:Overview: techniques and indications of LDL-apheresis. 175 62

The effect of estrogen and progesterone replacement therapy on the initiating events in atherogenesis was studied in surgically postmenopausal cynomolgus monkeys. Monkeys were ovariectomized and divided randomly into two groups, one receiving 17 beta-estradiol and cyclic progesterone treatment (n = 9) and ovariectomized controls receiving no hormone replacement therapy (n = 8). The monkeys were fed a moderately atherogenic diet for 18 wk to accelerate the early pathogenic processes but not to be of sufficient duration to produce grossly visible atherosclerotic lesions. Sex hormone replacement therapy decreased the accumulation of LDL and products of LDL degradation in the coronary arteries by greater than 70% while having no significant effect on plasma lipid, lipoprotein, or apoprotein concentrations. Arterial intimal lesions were small with no difference between groups. The reduction in arterial LDL metabolism occurred very early in the pathogenesis of atherosclerosis and was independent of indices of endothelial cell injury, such as enhanced endothelial cell turnover or leukocyte adhesion to the endothelium. Results of this study suggest that one mechanism by which sex hormone treatment inhibits the initiation of atherosclerosis is a direct effect at the level of the arterial wall by suppressing the uptake and/or degradation of LDL.
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PMID:Estrogen and progesterone replacement therapy reduces low density lipoprotein accumulation in the coronary arteries of surgically postmenopausal cynomolgus monkeys. 175 58

The development of atherosclerotic plaques is assessed as a result of interaction between modified apoprotein-B-containing lipoproteins and the cells of a vascular wall. The immune inflammation in atherosclerosis is considered, on the one hand, as a result of sensibilization to the modified lipoproteins, and, on the other, as a protective-adaptive reaction directed at the elimination of atherogenic lipoproteins from the vascular wall. The author's approaches to the treatment of atherosclerosis are based on the pathogenesis taking into consideration the role of macrophages in the lipid elimination from the plaques.
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PMID:[Current aspects of pathogenesis of atherosclerosis]. 177 56

The effect of gemfibrozil treatment (900 mg/day) on serum levels of total cholesterol, HDL-cholesterol, triglyceride, apoproteins A-I, A-II and B as well as HMG-CoA reductase in mononuclear cells was studied in patients with hyperlipoproteinemia types IIa and IIb. After 4 weeks of treatment gemfibrozil reduced total serum cholesterol (IIa: -17%, IIb: -26%), triglyceride (IIa: -39%, IIb: -47%) and apoprotein B (IIa: -22%, IIb: -15%). HDL cholesterol was increased by 20-22% and apoproteins A-I and A-II by 4-11%. Concomitantly, HMG-CoA reductase activity in freshly isolated mononuclear cells was suppressed by 78% in type IIa and 51% in type IIb patients. Continuation of treatment for up to 16 weeks prompted a further decline to 8 and 5% of the initial values, respectively. However, gemfibrozil failed to affect HMG-CoA reductase directly in homogenized or cultured mononuclear cells and did not further promote the suppressive action of LDL when added to the culture medium. Similarly, preincubation with the drug did not significantly modulate the binding or degradation of LDL in the cultured cells. However, LDL from patients with hyperlipoproteinemia types IIa and IIb exhibited enhanced binding and more potent HMG-CoA reductase suppression when isolated after compared to before gemfibrozil treatment. It is suggested that the HMG-CoA reductase inhibition observed in mononuclear cells during gemfibrozil treatment is due to changes in LDL structure affecting LDL receptor binding rather than direct effects of the drug on cellular cholesterol metabolism.
Atherosclerosis 1991 Dec
PMID:Inhibition of HMG-CoA reductase in mononuclear cells during gemfibrozil treatment. 178 8

Lipid and apoprotein composition of four very low density lipoprotein (VLDL) subfractions decreasing in Sf value were evaluated in the fasting state in 12 normolipidemic Pima Indians (6 M, 6 F, age 39 +/- 1.7 yrs) (mean +/- SEM) with non-insulin-dependent diabetes mellitus (NIDDM) in poor glycemic control (HbA1 9.8 +/- 2.9%) and in 14 normoglycemic Pima controls matched for age, BMI and lipid values. Total cholesterol (CHOL), triglyceride (TG), phospholipids (PL), total protein (TP), apo B, apo CII, apo CIII and apoE were assayed in total VLDL and in each of the four VLDL subfractions designed as A (Sf greater than 400), B (Sf 175-400), C (Sf 100-175), and D (Sf 20-100). Diabetics compared to nondiabetics had higher concentrations of all constituents of VLDL D, with the largest changes being in TG (38.0 +/- 3.8 vs 28.0 +/- 2.5 mg/dl, P less than 0.04), PL (14.0 +/- 1.3 vs 10.0 +/- 1.0 mg/dl, P less than 0.04), TP (9.8 +/- 0.8 vs 7.6 +/- 2.4 mg/dl, P less than 0.05), apo B (6.3 +/- 0.5 vs 4.7 +/- 0.4 mg/dl, P less than 0.03) and apoE (0.73 +/- 0.09 vs 0.52 +/- 0.04 mg/dl, P less than 0.04). Since no difference was found between the groups in percentage composition of lipids or apoproteins in total VLDL and in all VLDL subfractions, the data suggest that in diabetics, even when normolipidemic, there is an increase in the number rather than in the composition of the smallest VLDL subfraction (VLDL D), which are usually considered to be more atherogenic.
Atherosclerosis 1991 Nov
PMID:Alterations in very low density lipoprotein subfractions in normotriglyceridemic non-insulin-dependent diabetics. 181 50

The plasma concentration of lipoprotein (a) [Lp(a)] is correlated with the risk of atherosclerosis. It is a lipoprotein particle consisting of apoprotein (a) [Lp(a)] is correlated with the risk of atherosclerosis. It is a lipoprotein particle consisting of apoprotein (a) [apo(a)], a protein showing considerable amino acid sequence identity with plasminogen. bound to low-density lipoprotein. The apo(a) portion of Lp(a) was recently shown to have serine-proteinase-type amidolytic activity and to be able to degrade the adhesive glycoprotein fibronectin. To characterize this enzyme activity further, we used chromogenic peptide substrates and inhibitors. Of the substrates tested, those with arginine at the scissile bond [N-alpha-benzoyl-L-Arg p-nitroanilide (pNA), N-alpha-benzoyl-Ile-Glu-Gly-Arg-pNA, N-alpha-benzyloxycarbonyl-Arg-Gly-Arg-pNA] gave the highest hydrolysis rates. Synthetic substrates with plasmin specificity (Val-Leu-L-Lys-pNA and Val-Phe-L-Lys-pNA) were not hydrolysed by Lp(a). Neither tissue plasminogen activator nor urokinase had any effect on the enzyme activity. The addition of antibodies to these plasminogen activators did not inhibit the enzyme activity of Lp(a). Inhibition experiments with phenylmethanesulphonyl fluoride, carbodi-imide, dichloroisocoumarin and competitive peptide inhibitors demonstrated that Lp(a) has enzyme activity that closely resembles that of serine proteinases. Whether this serine-proteinase activity of Lp(a) plays any role in the genesis of atherosclerosis remains to be established.
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PMID:Characterization of the enzyme activity of human plasma lipoprotein (a) using synthetic peptide substrates. 182 80

A high plasma concentration of lipoprotein(a) [Lp(a)], a complex of low-density lipoprotein linked by disulphide bridges to apoprotein(a), is correlated with premature atherosclerosis. We determined whether the serum Lp(a) concentration could be decreased in vitro and in vivo by the reducing agent N-acetylcysteine (NAC), a drug used as a mucolytic agent, which acts by cleaving disulphide bonds. High concentrations of NAC (greater than or equal to 8 mg ml-1) resulted in dissociation of the Lp(a) antigen in vitro. However, the plasma level of Lp(a) was not changed by administration of NAC 1.2 g d-1 for 4 weeks in 7 subjects with a median Lp(a) concentration of 14.3 mg dl-1 (range 2.1-21.0 mg dl-1) or by doubling the dose to 2.4 g d-1 for a further 2 weeks. In 12 subjects with a high plasma level of Lp(a), median 87.0 mg dl-1 (range 42.0-201.6 mg dl-1), a small but significant decrease in Lp(a) concentration of 7% (P = 0.02) was observed after administration of NAC in a dose of 1.2 g d-1 for 6 weeks. These results indicate that NAC has only a limited capacity to reduce the concentration of Lp(a), which is not clinically significant.
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PMID:N-acetylcysteine and serum concentrations of lipoprotein(a). 183 21

Atherosclerosis is the main cause of mortality in diabetic patients, and the incidence of coronary heart disease is increased in the presence of microalbuminuria. The mechanisms of this association are not known and could involve genetic factors (predisposition to hypertension), renal disease and dyslipidemia. An increase in plasma triglyceride and apoprotein B levels, a decrease in plasma HDL cholesterol, qualitative abnormalities of VLDL and HDL are related to cardiovascular risk in diabetic patients. All these factors are worsened by nephropathy. Lipoproteins abnormalities could be involved in the progression of renal injury. In microalbuminuric patients, it seems important to reduce glomerular hyperfiltration and to normalize glycemia and blood pressure in order to prevent impairment of renal injury and dyslipidemia induced by nephropathy. Early treatment of lipoprotein abnormalities could decrease the incidence of cardiovascular complications.
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PMID:[Association of atherosclerosis and nephropathy in diabetes mellitus. Role of lipid anomalies]. 183 72

High-density lipoproteins (HDL) are now currently subdivided according either to density and size-HDL2 and HDL3--or to surface apoprotein composition--lipoprotein A-I (LpA-I) without A-II, and LpA-I:A-II. In samples from blood bank donors (60 women, 47 men), we evaluated HDL subclasses, LpA-I particles, and other classic risk factors for atherosclerosis and compared them with each other. We found a good correlation between HDL2 and LpA-I (r = 0.74, P less than 0.001), the correlation being more marked in women (r = 0.74) than in men (r = 0.67). LpA-I was also strongly correlated with total apolipoprotein A-I (apoA-I) (r = 0.61), which suggests that LpA-I represents a significant portion of the variable pool of apoA-I. By contrast, LpA-I:A-II but not LpA-I was correlated with HDL3, confirming the preferential association of LpA-I with HDL2. The difference between the sexes was more marked for HDL2 (+66% in women) than for LpA-I (+25%). We conclude that in normolipemic subjects the size of the HDL2 pool depends on that of LpA-I. Considering the speed and low cost of the assay, determination of HDL2 cholesterol might be a useful tool for assessing cardiovascular risk.
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PMID:Concentrations of high-density lipoprotein subfraction HDL2 and lipoprotein A-I in a random population of healthy subjects. 183 46


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