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)

Lipoprotein(a) denotes cholesterol-rich particles similar to low density lipoproteins but characterized by an extra large hydrophilic glycoprotein, Apo(a), added to low density lipoproteins. Apolipoprotein(a) is bound to ApoB-100 by a disulfide bridge. Eleven different Apo(a) isoforms of varying sizes coded for by alleles at the Apo(a) gene locus on chromosome 6 have been identified, ranging in Mr between roughly 400-800 kDa. The level of lipoprotein(a) is inversely correlated with isoform size. A strong independent association between high lipoprotein(a) levels and atherosclerotic disorders is documented. Lipoprotein(a) is selectively retained in the intima and engulfed by macrophages in unmodified form. Human Apo(a) is very similar to plasminogen, which suggests that lipoprotein(a) represents a link between atherosclerosis and thrombosis.
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PMID:Lipoprotein(a), atherosclerosis and thrombosis. 184 Apr 53

Increased cholesterol levels above 200 mg/dl, LDL levels above 130 mg/dl and total cholesterol/HDL ratio above 4.5 in males and above 5.0 in females are recognized as indicators of increased risk of atherosclerosis. Risk associated to increased triglyceride levels (above 200 mg/dl) must be judged in relation to associated factors such as family history of coronary heart disease, presence of remnants (type III hyperlipidemia), presence of Lp(a), increased levels of Apo B, reduced levels of HDL2 or Apo A1. VLDL and chylomicron remnants and Lp(a) have an atherogenic power in vitro 2 to 4 times that of LDL. There is a correlation between hypertriglyceridemia and reduced HDL2 and Apo A1 levels. Hypertriglyceridemia is frequently associated to other risk factors like diabetes, obesity, hyperinsulinism, and high blood pressure. Finally, VLDL may elevate levels of plasma plasminogen inhibitor. Thus, hypertriglyceridemia should be investigated when, evaluating risk of atherosclerosis.
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PMID:[Cholesterol and triglycerides in atherosclerosis: epidemiologic and physiopathologic considerations]. 184

Among the risk factors for atherosclerosis, lipoproteins play a central role, particularly in the development of coronary artery disease. The plasma cholesterol level was the first definite indicator of the risk factor. Thereafter, technical progress has permitted the measurement of the cholesterol fractions, LDL cholesterol which is positively correlated with atherosclerosis, and HDL cholesterol, which is protective. However, the measurement of these fractions in a subject does not permit accurate determination of the risk to the subject. Likewise the measurement of apo A-I and B has brought an improvement in determining the risk factor but is still insufficient. The clarification of new markers would allow better definition of the potential atherogenic risk to a given individual Lp A-I (lipoproteins containing apo A-I but not apo A-II) level is probably an important indicator. Similarly, Lp(a) level is certainly an atherogenic lipoprotein and the apo E phenotype modulates the development of atherosclerosis. All these new markers and others, in the future, will better define the risk for an asymptomatic subject, with regard of atherosclerosis and therefore help to prevent it.
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PMID:[From cholesterol to lipoprotein particle markers and/or risk factors]. 186 58

The major components of atherosclerotic plaque, ultimately responsible for clinical effects, are deposited lipids--mostly cholesteryl esters and cholesterol, derived largely from the lower-density lipoproteins of the blood--and proliferated, modified arterial smooth muscle cells with their synthesized connective tissue products. Advanced plaques vary widely in the proportion of the two components, but evidence indicates that lipid deposition--especially of lipoprotein elements--often occurs in the lesion-prone intimal areas of the artery prior to the buildup of smooth muscle cells. The 1980s were remarkably productive for investigators who study the pathogenesis of atherosclerosis. We now know of the many forms of lower-density lipoproteins, i.e., low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL), some of which are more likely to be associated with accelerated atherosclerosis and some of which are more likely to be influenced by diet. Among these forms of LDL and VLDL are LDL-1, beta-VLDL, and Lp(a). Work has been reported implicating various alterations of endothelial function in the permeability of the arterial endothelial barrier in the transport of these low-density, cholesterol-rich macromolecules. Of possibly greater interest is the developing evidence that such proliferation-stimulating molecules as platelet-derived growth factor (PDGF) can be produced by a number of cells likely to be involved in the progression of atherosclerotic plaque. In addition to platelets, these include activated monocytes and monocyte-derived macrophages, injured endothelial cells, and smooth muscle cells, which can undergo an autocrine conversion to PDGF synthesis--possibly stimulated by LDL from hyperlipidemic serum. Leukotrienes and other endothelium-associated regulatory molecules may also take part in the paracrine and autocrine mechanisms of stimulating smooth-muscle-cell proliferation. Additional recent developments that have led to a better understanding of atherosclerotic pathogenesis have occurred. The first is evidence of the involvement of oxidized LDL and its apolipoprotein B in atherogenesis. Research indicates that antioxidants have a suppressive effect on atherogenesis when oxidized LDL has been involved in lesion development. The data linking the development of autoimmune reactions to these oxidatively altered lipoproteins are also impressive. Further, there is increasing evidence that atherogenesis in nonhuman primates and in people in whom chronic sustained circulating immune complexes are involved is likely to be accelerated, even when few or no classic risk factors are present. These lesions appear to represent a distinct microarchitectural form of concentric and transmural atherosclerosis that is better classified as "atheroarteritis."
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PMID:Update on the pathogenesis of atherosclerosis. 186 33

HMG-CoA reductase inhibitors have been proven effective in decreasing the plasma cholesterol levels in patients affected with various forms of hypercholesterolemia, familial dysbetalipoproteinemia, familial combined hyperlipidemia and in nephrotic and diabetic dyslipidemia. The purpose of this study was to monitor and evaluate the efficiency and safety of the therapy with simvastatin, an HMG-CoA reductase inhibitor, in a group of patients treated by continuous ambulatory peritoneal dialysis (CAPD) with severe hypercholesterolemia. Monitoring of the changes occurring in the various lipids and apolipoproteins in these patients included the measurements of the plasma lipids and apolipoproteins A-I, A-II, B, C-II, A-IV and Lp(a). Lipoproteins were separated by gel filtration, on a Superose 6HR column, before and after 24 weeks of treatment. The patterns were compared to those observed in a group of primary hyperlipidemic patients treated with Lovastatin, a compound of the same class. The drug was well tolerated by the CAPD patients and no adverse reaction was observed. In addition to the decrease of the total and LDL cholesterol, similar to that reported in other groups of patients, we further observed a decrease of the apo E concentration in both the CAPD and the hyperlipidemic patients. This decrease was especially pronounced in the HDLE fraction and could involve an upregulation of the apo B-E and/or apo E receptor. These results should provide information about the mechanism of action of this drug in patients with end-stage renal disease.
Atherosclerosis 1991 Feb
PMID:Effect of simvastatin treatment on the dyslipoproteinemia in CAPD patients. 187 12

Endothelial cells play a critical role in thromboregulation by controlling the assembly of fibrinolytic constituents on the membrane. The assembly system illustrated in FIGURE 6 is characterized by the binding of circulating glu-plasminogen to a membrane receptor (Pathway 1). A membrane-associated protease (possibly plasmin) converts the inactive zymogen into a catalytically more efficient zymogen lys-plasminogen (Pathway 2). T-PA binds to a specific receptor, retains its catalytic activity, and is protected from its natural inhibitor PAI-1. The membrane provides a favorable environment for plasmin generation (Pathway 3) at the vessel surface and contributes to the maintenance of a physiological nonthrombogenic state. The immobilization and surface activation of plasminogen provides an important mechanism for localizing proteolytic activity at the surface of other cells such as macrophages and tumor cells. Lp(a), a plasminogen-like lipoprotein, by competing at the endothelial surface for plasminogen binding down-regulates endothelial cell plasmin generation and may thus promote localized thrombogenesis that over a period of time contributes to progressive atherosclerosis.
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PMID:Endothelial cell fibrinolytic assembly. 190 39

Patients with insulin-dependent diabetes mellitus (IDDM) have a significantly increased risk of macrovascular disease, particularly if they have persistent proteinuria. To determine whether altered levels of apolipoprotein(a) [apo(a)], the plasminogenlike glycoprotein of the potentially atherogenic lipoprotein(a); contribute to the increased risk of atherosclerosis, apo(a) levels were measured in 107 patients with IDDM and compared with nondiabetic control subjects and male elective coronary artery graft patients. Apo(a) levels were increased in diabetic patients with microalbuminuria (geometric mean 245 U/L, 95% confidence interval [CI] 142-427, n = 30) and albuminuria (mean 196 U/L, 95% CI 97-397, n = 18) with levels comparable to patients with coronary artery disease (mean 193 U/L, 95% CI 126-298, n = 40), which were higher than in the control group (mean 107 U/L, 95% CI 85-134, n = 140; P = 0.016). Apo(a) levels in diabetic patients without microalbuminuria (mean 86 U/L, 95% CI 63-116, n = 59) were comparable with the control population and less than in those with microalbuminuria (P less than 0.001) and albuminuria (P = 0.014). The elevated apo(a) levels found in patients with IDDM and increased urinary albumin loss may contribute to their heightened risk of macrovascular disease.
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PMID:Increased plasma apolipoprotein(a) levels in IDDM patients with microalbuminuria. 204 Mar 96

LDL-apheresis (immunoabsorption, heparin precipitation (HELP), dextran sulfate cellulose binding (DSC) or filtration) is a potent therapeutic tool in familial hypercholesterolemia (FH) to eliminate LDL-cholesterol, Lp(a) or fibrinogen from the circulation and improve blood rheology. Repetitive use can deplete the cholesterol pool between 40 and 80%. As first reports showed, progression of coronary atherosclerosis can be stopped and sometimes regression can be induced. So far the domain of plasmapheresis was homozygous familial hypercholesterolemia. With several apheresis methods now available, it seems timely to define the indication of plasma therapy for heterozygous FH and the place of this potent therapeutic tool in primary and secondary prevention of atherosclerotic coronary heart disease in patients suffering from severe hypercholesterolemia resistant to diet and/or drug therapy.
Atherosclerosis 1991 Jan
PMID:LDL-apheresis: results of longterm treatment and vascular outcome. 206 31

Lipoprotein(a) [Lp(a)] is a low-density lipoprotein (LDL)-like lipoprotein particle recently described as a risk factor for premature coronary heart disease, stroke, and atherosclerosis. Structurally, Lp(a) is similar to LDL in that it has comparable lipid composition and contains apolipoprotein B-100 (apo B-100). In addition, Lp(a) contains the glycoprotein apolipoprotein(a) [apo(a)], which is disulfide-linked to apo B-100. The recent awareness of a striking correlation between atherosclerosis and concentrations of Lp(a) in plasma prompted our development of an accurate quantitative assay for plasma Lp(a), a monoclonal-antibody-based enzyme-linked immunosorbent assay for Lp(a) that is shown to be sensitive, precise, and highly specific. The response to several isoforms of Lp(a) is linear, and as many as 80 samples can be quantified on one plate. This easily performed assay is suitable for use in the clinical laboratory and for screening large populations.
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PMID:A monoclonal-antibody-based enzyme-linked immunosorbent assay of lipoprotein(a). 213 83

Lipoprotein Lp(a) is a plasma lipoprotein which possesses many similarities to low density lipoprotein (LDL) in its physical and chemical properties. The major protein constituent of both lipoproteins is apolipoprotein B100 (apo B100); however, Lp(a) is unique in that it contains an additional distinct antigen, the (a)-antigen, attached to apo B100 by one or more disulphide bridges. The (a)-glycoprotein has recently been shown to have a striking amino-acid sequence homology with plasminogen; so, Lp(a) seems to be a potential bridge between the fields of atherosclerosis and thrombosis. Metabolic studies have made it clear that Lp(a) is not a product derived from other apo B-containing lipoproteins, but is secreted by the liver as a distinct mature lipoprotein. Although a relationship between elevated serum Lp(a) levels and the occurrence of atherosclerotic diseases had been postulated by several investigators, little is known today about the role of this lipoprotein and/or the mechanism whereby it might predispose to atheroma. However, the new knowledge on the structure of Lp(a) being more and more rapidly acquired, should facilitate the understanding of the mechanism of its atherogenicity and its physiopathological role.
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PMID:[Lipoprotein (a). An additional marker of atherosclerosis]. 214 Dec 41


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