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)

In previous studies, it was shown that a lysine deficient diet reduces the severity of aortic cholesterol atherosclerosis in rabbits. Feeding 1-amino-3-imino N,N' propene diacetate (AIPD) produced 2 metabolic by products with active aldehyde groups 1-amino propenal acetic acid (APA) and malonyldialdehyde (MDA) that transiently block the lysine epsilon-amino groups of all proteins and lipoproteins in vivo. This paper reports the effects of blocking the lysine free epsilon-amino groups of all lipoproteins on 2 different types of cholesterol atherosclerosis; (1) A proliferative-type cholesterol atherosclerosis containing a high proportion of spindle-shaped myogenic foam cells rich in collagen and alcian blue-stainable material produced by feeding a diet containing cholesterol, peanut oil, ethanol and butylated hydroxyanisole and (2) cholesterol atherosclerosis containing a high proportion of polyhedral-shaped nonmyogenic macrophage-type foam cells produced by feeding cholesterol and oleic acid. After 14 weeks on the diets the mean +/- SD percent of intimal aortic area covered with the myogenic-type atherosclerosis in the control peanut oil-fed group was 34 +/- 6% and this was reduced to 13 +/- 3% in the peanut oil AIPD group. In contrast, after 14 weeks in the control oleic acid group the severity of atherosclerosis was 14 +/- 4% and this was increased to 36 +/- 7% in the oleic acid AIPD group. Aortic cholesterol concentration was decreased in the AIPD peanut oil group relative to its control but was increased in the AIPD oleic acid group relative to its control group. A higher concentration of AIPD metabolites accumulated in the atherosclerotic lesions of the oleic AIPD group than in the peanut oil AIPD group indicating that a larger amount of lysine blocked lipoprotein accumulated in the macrophage-rich lesions of the oleic acid AIPD group than in the myogenic-rich lesions of the peanut oil AIPD group. Blocking lysine epsilon-amino groups in vivo by feeding AIPD did not modify DNA synthesis in the aortae of either AIPD group relative to their control groups.
Atherosclerosis 1985 Oct
PMID:Modification of two types of cholesterol atherosclerosis in rabbits by blocking lipoprotein lysine epsilon-amino groups. 393 26

Patients with renal failure on maintenance hemodialysis have accelerated rate of atherosclerosis. This, and the fact that chemically modified low-density lipoproteins (LDL) have a better capacity than native LDL to stimulate cholesteryl ester accumulation within macrophages in the vessel wall, led us to examine the possibility that some alteration in apo-LDL may take place in chronically uremic patients. We isolated LDL (d = 1.019 - 1.063 g/mL) from 18 patients with chronic renal failure and from 13 normolipidemic controls and compared the interactive properties of the different LDL preparations with cultured fibroblasts. Our results show that "uremic" LDL associates less, is degraded less, and has diminished ability to stimulate cholesteryl ester formation in fibroblasts when compared to normal LDL. LDL carbamylated in vitro showed interactive properties with fibroblasts similar to those of uremic LDL. Uremic LDL was not taken up by scavenger receptors present on rat peritoneal macrophages, similarly to normal LDL. However, the decrease in uptake by fibroblasts of uremic LDL may increase the residence time of these particles within the subendothelial region of the vessel wall, ultimately resulting in increased atherogenicity. Carbamylation of lysine residues of apoB in vivo, abnormal catabolism of LDL due to the absence of functional renal tissue, or triglyceride enrichment of LDL are among the possible explanations for the abnormal properties of uremic LDL.
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PMID:Abnormal cell-interactive properties of low-density lipoproteins isolated from patients with chronic renal failure. 396 57

Elastin preparations from intimal layers and the media of normal and atherosclerotic human aortae were analyzed for protein and lipid content. In atherosclerotic aortae, elastin from plaques was compared with elastin from adjacent normal appearing areas of the same aorta. Arterial elastin purified by alkaline extraction appeared to be a protein-lipid complex containing free and ester cholesterol, phospholipids, and triglycerides. The lipid component of normal arterial elastin was small (1-2%). With increasing severity of atherosclerosis, there was a progressive accumulation of lipid in intimal elastin from plaques, reaching a mean lipid content of 37% in severe plaques. The increase in the lipid content of plaque elastic preparations was mainly due to large increases in cholesterol, over 80% of which was cholesteryl ester. This deposition of cholesterol in plaque elastin accounted for 20-34% of the total cholesterol content of the plaque. The increased lipid deposition in plaque elastin was associated with alterations in the amino acid composition of plaque elastin. In elastin from plaque intima, the following polar amino acids were increased significantly: aspartic acid, threonine, serine, glutamic acid, lysine, histidine, and arginine; whereas, cross-linking amino acids: desmosine, isodesmosine, and lysinonorleucine were decreased significantly. The amino acid and lipid composition of elastin from normal appearing aortic areas was comparable to that of normal arterial elastin except for intimal elastin directly adjacent to and medial elastin directly below the most severe plaques.The data indicate that the focal lipid deposition in early atherosclerotic plaques is due to a large extent to lipid accumulations in altered elastin protein of localized intimal areas. Continued lipid deposition in altered elastin appears to contribute substantially to the progressive lipid accumulation in the plaque. The study suggests that elastin of intimal elastic membranes may play an important role in the pathogenesis and progression of atherosclerosis.
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PMID:The protein and lipid composition of arterial elastin and its relationship to lipid accumulation in the atherosclerotic plaque. 509 73

The effect of varying the compositions of dietary proteins on the relative cholesterolaemic effects of animal and vegetable proteins was investigated in rabbits. In experiments using high fat diets, the amino acid compositions of dietary proteins (soya or casein) were altered by blending them 1:1 (w/w) with gelatin. This reduced the differences in amino acid compositions and also made soya more and casein less hypercholesterolaemic. In experiment 2a, soya protein was compared with dried skim milk in low fat diets and in experiment 2b, these proteins were supplemented with lysine or arginine, respectively, so that the lysine:arginine ratio of soya was similar to dried skim milk and vice-versa. Serum cholesterol was significantly higher in milk-fed than soya-fed rabbits and was not influenced by reversing the lysine:arginine ratio. In the three experiments, parameters of cholesterol kinetics were estimated from the die-away curve of injected [4 14-C]cholesterol. There were no significant effects of diet on the parameters of cholesterol kinetics. It was concluded that the lysine:arginine ratio of the diet is not the major determinant of the cholesterolaemic properties of proteins, but that the overall amino acid composition is primarily concerned.
Atherosclerosis 1983 Jun
PMID:The effect of dietary lysine to arginine ratio on cholesterol kinetics in rabbits. 641 Oct 98

Modifications of plasma lipoprotein structure and function resulting from in vivo post-translational nonenzymatic glycosylation may play a role in the premature atherosclerosis of patients with diabetes mellitus. This report describes the generation and characterization of six unique murine monoclonal antibodies that bind glucosylated human plasma lipoproteins, but do not react with normal plasma lipoproteins. This was accomplished by immunizing mice with homologous glucosylated low density lipoprotein. In competitive inhibition radioimmunoassays, the dominant epitope recognized by these antibodies on glucosylated low density lipoprotein was identified as glucitollysine, the reduced hexose alcohol form of glucose conjugated to the epsilon amino group of lysine. Each of these antibodies was capable of identifying glucitollysine epitopes on all reduced glucosylated proteins studied, including high density lipoprotein, albumin, hemoglobin, and transferrin. These antibodies were also capable of identifying and quantitating glucitollysine residues on the total plasma proteins and isolated lipoproteins of normal and diabetic individuals after reduction of the proteins with NaBH4. Preliminary data suggest that diabetic total plasma proteins and isolated lipoproteins contain at least threefold more immunochemically detectable glucitollysine residues than nondiabetic plasma proteins and lipoproteins. The technique described in this report should allow production of region-specific antibodies to any immunogenic modification of a protein.
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PMID:A novel method for generating region-specific monoclonal antibodies to modified proteins. Application to the identification of human glucosylated low density lipoproteins. 641 10

Porcine aortic endothelium cultured at 20% oxygen concentration synthesizes collagen and three of its marker enzymes - proline and lysine hydroxylases and lysine oxidase, the cross-link enzyme. It also synthesizes and secretes hyaluronic acid, dermatan sulphate, possibly heparan sulphate, large amounts of chondroitin 4-sulphate and smaller amounts of chondroitin 6-sulphate. Growth of these cells for 24 h in 0%, or 2% oxygen results in little change in cell numbers or cell protein but a fall in collagen synthesis and in proline and lysine hydroxylases, but a rise in lysine oxidase. There is a considerable increase in synthesis and secretion of all the glycosaminoglycans found. The cell lipids appear qualitatively unchanged. Apart from increased lysosomes seen at 0% oxygen, no ultrastructural changes appear to occur. These findings illustrate the lability of the endothelial response to oxygen lack.
Atherosclerosis 1982 Sep
PMID:The effect of hypoxia on the synthesis of collagen and glycosaminoglycans by cultured pig aortic endothelium. 681 51

Human low-density lipoprotein (LDL) was glucosylated by incubation in vitro with glucose (20-80 mM) with or without addition of cyanoborohydride. The incorporation of covalently bound glucose was linear over time, and amino acid analysis showed the presence of glucosyllysine residues. The glucosylated LDL (glc LDL) moved more rapidly than normal LDL on agarose electrophoresis. The rate of degradation of 125I-labeled glucosylated LDL (glc LDL) by cultured human fibroblasts was reduced compared with that of native I-LDL, the difference increasing with extent of glucosylation. Effects were seen with blockage of as few as 6-15% of the LDL lysine residues; high-affinity degradation was completely lost when one-third of the lysine residues were blocked. Conjugation of LDL with glucose-6-phosphate also blocked high-affinity uptake and degradation. Whereas native LDL uptake inhibited the activity of beta-hydroxy-beta-methylglutaryl coenzyme A reductase and stimulated acyl coenzyme A:cholesterol acyltransferase activity, glc LDL had no effects on these enzymes. The fractional catabolic rate of glc LDL in guinea pigs was reduced. Degradation of glc LDL by mouse peritoneal macrophages was not significantly faster than that of native LDL. Finally, the presence of glc LDL in human plasma was demonstrated. Preliminary data show that 1.3% of lysine residues in normal LDL and 2-5.3% of lysines in diabetic LDL were glucosylated. Since, like other plasma proteins, LDL undergoes glucosylation in diabetes, its turnover and sites of catabolism may differ from normal and this may be relevant to the accelerated atherosclerosis of diabetes.
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PMID:Nonenzymatic glucosylation of low-density lipoprotein alters its biologic activity. 681 75

This review deals with some structural features of the collagen molecules involved in the adhesion of platelets representing the initial step of hemostasis, thrombosis, and (partly) atherosclerosis. The adhesion occurs at the level of a vascular lesion or deendothelialized area, whatever the genetic type of collagen. In vitro experiments with purified collagens have shown that vascular interstitial collagens (types I and III, the latter present in subendothelium) as well as basement membrane-derived collagens (types IV and V) induce an adhesion of platelets, provided that an ordered arrangement linked to the quaternary and tertiary structures of their molecule is preserved. Whatever the quaternary structure, the important point seems to be the size of the fibers and more precisely the availability of an optimal number of adhesion sites on multimerized fibers. Various direct or indirect proofs (for example, the occurrence of the impairment of collagen multimerization on platelet adhesion/aggregation) are reviewed. Our recent studies on interstitial collagens have shown the involvement of certain specific amino-acid sequences obtained after cyanogen bromide cleavage of collagen. These are the C-terminal alpha1 (I) CB6 peptide of the alpha 1 chains of type I collagen (216 amino acids) and the central alpha1 (III) CB4 peptide from type III collagen (149 amino acids) Cleavage of this last peptide by chymotrypsin, hydroxylamine, and trypsin has suggested the possibility that a nonapeptide (sequence gly-lys-hyp-gly-glu-hyp-gly-pro-lys) is a minimum site of adhesion for platelets. This assumption has been reinforced by the fact that a synthetic nonapeptide with this sequence specifically inhibits the aggregation of platelets to collagen in vitro. The adhesion of platelets may consequently be due to the repetitive staggering of short amino acid sequences (such as this nonapeptide from type III collagen) along the rigid structure formed by a multimerized collagen fiber.
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PMID:[The adhesion of blood platelets to collagen: molecular features of collagen (author's transl)]. 702 81

The COOH-terminal BrCN fragment of the aldolase alpha-subunit from muscles of rabbits in norm and under atherosclerosis was studied by the method of dansyl-fingerprints in a silicagel and polyamide thin layer. It is shown that under atherosclerosis the amount of peptides in the fragment under study increases and the topography of two of them changes. The content of lysine, serine and valine enhances in it. The results evidence for structural differences in C-terminal fragment of aldolase alpha-subunits in muscles of rabbits in norm and under experimental atherosclerosis.
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PMID:[Structural differences of C-terminal fragment of the alpha-subunits of rabbit muscle aldolase in normal animals and in experimental atherosclerosis]. 713 8

Under atherosclerosis the fractions corresponding to alpha-subunits are focused at a more alkaline pH than the same fractions in the norm. The curve of the enzymic activity of the fractions with atherosclerosis is higher. beta-subunits of aldolase from muscles of intact rabbits and those with sclerosis are identical in the amino acidic composition. In the enzyme alpha-subunits under conditions of atherosclerosis the content of lysine, serine, glycine, valine gets higher. On the basis of the previous research which reveals peptide having no analogs in the norm in the C-terminal fragment of aldolase molecule an assumption is advanced that under conditions of atherosclerosis the intermediate C-terminal site of the enzyme alpha-chain changes.
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PMID:[Amino acid composition and subunit structure of rabbit muscle aldolase in experimental atherosclerosis]. 721 Feb 25


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