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)

The catabolism of low-density lipoproteins (LDL), the major cholesterol-carrying lipoproteins in plasma, is mediated in part via a high-affinity uptake pathway in the liver. Non-enzymatic glucosylation of lysine residues of apolipoprotein B, the major protein of LDL, blocks receptor-mediated uptake of LDL by fibroblasts and endothelial cells. We investigated the effect of the degree of glucosylation on the binding, uptake and degradation of radioiodinated LDL by the human hepatoma cell line Hep G2. Human LDL was glucosylated with 250 mM glucose and 30 mM cyanoborohydride at 37 degrees C. Incubations ranging from 3 to 48 h in duration resulted in the formation of 6-27% of glucitol-lysine adducts as demonstrated by coincubation with [14C]glucose. The degree of glucose incorporation corresponded to the extent of inhibition of binding, uptake and degradation of LDL (10-90%). The data are consistent with the view that glucosylation of LDL markedly impairs their catabolism. This phenomenon may be related to the pathophysiology of the premature atherosclerosis observed in diabetes mellitus.
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PMID:Impaired hepatocyte binding, uptake and degradation of glucosylated low-density lipoproteins. 301 18

To detect genetic mutants of apo A-I, the major structural protein of human HDL, we screened 530 unrelated Austrian probands (168 children, 362 adults). An apo A-I mutant characterized by an exchange of the acidic amino acid Glu in position 198 with the basic amino acid Lys was identified in the serum of the mother of a hyperlipoproteinemic girl. So far only two patients with this mutant, referred to as apo A-I (Glu 198----Lys) have been described. We detected six new patients (two children and four adults) with apo A-I (Glu 198----Lys) among 20 members in three generations of the affected family. An autosomal codominant inheritance of the apolipoprotein variant could be established. All affected individuals were heterozygous for the mutant. Among the six new subjects with apo A-I (Glu 198----Lys) two children and one adult presented with high-density lipoprotein (HDL) cholesterol concentrations below the fifth percentile for age and sex and with low serum apo A-I and A-II. Although there was no consistent relationship of the mutant with low serum HDL in this family, a moderate effect of apo A-I (Glu 198----Lys) on HDL levels cannot be ruled out. Hyperlipoproteinemia of types IIa, IIb, and IV was observed in eight of the 20 family members studied, but did not cosegregate with the mutant apo A-I. There was no association of apo A-I (Glu 198----Lys) with premature clinical manifestations of atherosclerosis. The mutation occurred in a part of the apo A-I molecule, which is thought to be involved in lipid binding.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Apolipoprotein A-I (Glu 198----Lys): a mutant of the major apolipoprotein of high-density lipoproteins occurring in a family with dyslipoproteinemia. 314 94

We investigated the effects on blood pressure of 5% taurine administered prenatally or postnatally via maternal parents in stroke-prone spontaneously hypertensive rats (SHRSP). Prenatal and/or postnatal administration of taurine produced a blood pressure reduction in the offspring until at least 3 months of age. Furthermore, offspring exposed to high concentrations of taurine through the placenta during the prenatal period and also for 1 month after birth via maternal milk, showed a greater reduction in blood pressure than the group given taurine prenatally but not postnatally. The stroke-prone SHR were fed a high-fat cholesterol and low-protein diet containing 1% methionine or with 3% lysine in drinking water, and effects of the dietary amino acids on the development of atherogenesis were investigated. Intake of additional 1% methionine or 3% lysine had marked preventive effects on atherogenesis in the cerebral and mesenteric arteries in SHRSP. Therefore, early dietary intake of sulphur amino acids delays the onset of hypertension and attenuates the development of both severe hypertension and atherosclerosis in SHRSP.
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PMID:Effects of sulphur amino acids on the development of hypertension and atherosclerosis in stroke-prone spontaneously hypertensive rats. 348 15

The availability of epsilon-lysine residues of apolipoprotein B in LDL for chemical or enzymic modification was investigated. Amino acid analyses of detergent-solubilized apolipoprotein B, following cyanoethylation with acrylonitrile, revealed that 10% of the lysine in apolipoprotein B were unreactive. The unreactive residues were associated with the most hydrophobic subfraction of apolipoprotein B. Since apolipoprotein B has a high molecular weight a study was undertaken to determine whether lysine residues were crosslinked to glutamic acid via epsilon-(gamma-glutamyl)lysine as demonstrated for fibrin. Apolipoprotein B was digested exhaustively with proteases. The content of epsilon-(gamma-glutamyl) lysine was determined by chromatography and isotope dilution. In contrast to earlier reports for serum LDL the data showed that less than 0.01 moles of lysine/mole of LDL apolipoprotein B were present as epsilon-(gamma-glutamyl)lysine in plasma LDL. It was determined also that the crosslinks were not found in apolipoprotein B during clotting since LDL was not a substrate for clotting factor XIII which forms the bond in fibrin. Furthermore, the lipoprotein contained no inherent transglutaminase activity. It is concluded that the lysine residues in LDL, which are unreactive to cyanoethylation, can not be detected in the digests as epsilon-(gamma-glutamyl)lysine.
Atherosclerosis 1986 Jul
PMID:The biochemistry of epsilon-amino groups of lysine residues from apolipoprotein B of human low density lipoprotein. 373 52

We have isolated an apolipoprotein B (apo B) clone (pXB1) from a human liver cDNA expression library, by immunoselection with a polyclonal antibody to human low density lipoprotein. pXB1 was used to isolate 3 clones (pB2, pB3 and pB4), containing cDNA inserts spanning a region of 3.75 kbp, from a second human liver cDNA library. We report the sequence of 1359 nucleotides at the 3' end of the pB4 cDNA insert and the amino acids encoded by this sequence. The cDNA inserts of pBX1 and pB2 overlapped the sequenced portion of pB4. pB2 contained an EcoR1 restriction site (resulting in a Glu-Lys replacement) which is not present in pB3 or pB4 and pB3 contained an MspI site not present in pB2 or pB4. Since all 3 clones were derived from the mRNA of a single human liver, we suggest that the human haploid genome contains more than one functional apo B gene. Labelled probes spanning almost the whole of the pB4 cDNA insert hybridized with RNA from human liver and small intestine, showing that the apo B mRNAs from these two tissues have nucleotide sequences in common. The nucleotide sequence in human liver apo B mRNA is probably longer than 12 kb, showing that the MW of monomeric apo B is at least 350kd. Clone pB4 hybridized with mRNA of similar length in rabbit liver and small intestine. These results raise the possibility that the low MW apo B synthesized in the intestine (B-48) and the high MW apo B synthesized in the liver (B-100) are translated from the same mRNA. The expression products of fragments of pB4 cloned into an expression vector were blotted with monoclonal antibodies to human LDL. The results suggest that the cDNA insert in pB4 encodes a part of apo B common to B-48 and B-100 and a region close to the recognition site for the LDL receptor.
Atherosclerosis 1985 Dec
PMID:Molecular cloning of human LDL apolipoprotein B cDNA. Evidence for more than one gene per haploid genome. 384 81

The effect of various chemical and enzymatic modifications of low density lipoprotein (LDL) on its ability to activate the isolated human plasma lysolecithin acyltransferase (LAT) was studied. Removal of all lipids from LDL resulted in the complete loss of LAT activation. Removal of only neutral lipids by extraction with heptane retained up to 50% of the original activity, which was not increased further by reconstitution of the LDL with the extracted lipids. Hydrolysis of the diacylphosphoglycerides of the LDL with phospholipases resulted in complete loss of LAT activation which was partially restored by the addition of egg lecithin. Hydrolysis of more than 4% of LDL protein by trypsin led to a linear decrease in activity with complete loss of activity occurring when about 25% of the LDL protein is hydrolyzed. Modification of the arginine groups of LDL reversibly inhibited the activation of LAT. Modification of lysine residues of LDL by acetylation, acetoacetylation or succinylation also abolished its ability to activate lysolecithin acylation.
Atherosclerosis 1985 Jan
PMID:Role of low density lipoprotein in the activation of plasma lysolecithin acyltransferase activity. Effect of chemical and enzymatic modifications of the lipoprotein on enzyme activity. 392 84

Rats fed a semipurified diet containing casein developed higher levels of circulating triglycerides and cholesterol than animals fed a soy protein-containing diet. The increased serum lipid levels in non-fasted rats were associated largely with the d less than 1.006 g/ml lipoprotein particles (e.g. chylomicrons or very low density-like lipoproteins). In addition, casein-fed rats exhibited higher levels of circulating insulin and depressed hepatic 7 alpha-hydroxylase levels compared to soy-fed rats. Supplementation of the casein diet with arginine, to give an arginine/lysine ratio comparable to that in the soy diet, resulted in a reduction of d less than 1.006 g/ml lipids, a reduction in serum insulin levels and an elevation in hepatic 7 alpha-hydroxylase activity. Supplementation of the soy diet with lysine also resulted in modification of these parameters toward those observed with casein diets, albeit the effects were less dramatic. The results suggest that the hyperlipidemia associated with feeding casein-based diet is associated with decreased rates of clearance of chylomicron-like lipoproteins and their component triglycerides and cholesterol. Furthermore, this is largely prevented by addition of arginine to diets containing casein as the sole protein source.
Atherosclerosis 1985 Aug
PMID:Effects of casein and soy protein on hepatic and serum lipids and lipoprotein lipid distributions in the rat. 393 24

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


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