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 small molecular weight apolipoproteins of pig very low density lipoprotein were investigated following their separation by gel filtration and ion exchange chromatography. Gel filtration through Sephadex G-200 in 6 M urea, produced essentially the same elution profile to that obtained after filtration of human very low density apolipoprotein. However, separation of the pig Sephadex fraction corresponding to human C proteins on DEAE-cellulose columns revealed the presence of only one major peptide and minor quantities of several others. Some properties of three apparent homogeneous fractions and one heterogeneous DEAE fraction were investigated. Unlike human apoprotein CII apoprotein, none of the pig peptides studied activated cow's milk lipase and sialic acid was not detected in any of the three purified C peptides of pig VLDL. The amino acid compositions of the pig peptides were different to those reported for human C apoproteins. The carboxy terminal residue of the major pig C peptide was shown to be serine. The differences so far revealed between pig and human C peptides need further investigation especially since this animal is regarded as a suitable model for investigating human lipoprotein metabolism and the development of atherosclerosis.
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PMID:Characterisation of the small molecular weight apolipoproteins from pig plasma very low density lipoprotein. 17 51

Electron microscopy of the reaction product between human pooled high density lipoprotein (HDL) and cholesterol shows that characteristic liposome macromicellar bodies are formed. These bodies vary in size between 30 and 1200 nm. In comparison with HDL, they contain markedly more cholesterol, but less protein and phospholipid. Their phospholipid pattern shows enrichment with sphingomyelin and phosphatidyl serine in comparison with HDL.
Atherosclerosis 1978 Dec
PMID:The action of human high density lipoprotein on cholesterol crystals. Part 2. Biochemical observations. 21 77

A significant increase of the relative phosphatidyl serine level, a decrease in the percentage of lipoleic and arachidonic acids, and an increase in the oleic acid level were revealed in blood platelet phospholipids of patients with ischemic heart disease and severe coronary atherosclerosis. In the entire group of patients with ischemic heart disease (with coronary atherosclerosis of various degree), these changes are less marked and only the decrease in the linoleic acid level as compared to that in healthy individuals is significant. It was established that besides these changes in the phospholipid structures, blood platelet aggregation increases when the severity of the atherosclerotic process in the coronary arteries becomes more pronounced.
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PMID:[Thrombocyte phospholipids in ischemic heart disease with a varying degree of coronary arteriosclerosis severity]. 43 12

A method is presented for grinding and extracting very small samples of tough fibrous tissue from single atherosclerotic lesions of human aortas. Grinding to a powder was easily accomplished while the samples were frozen in liquid nitrogen in a porcelain micromortar. Extractions of the powder were made first in the mortar and then in tapered centrifuge tubes. Salt soluble, dodecyl sulfate--mercaptoethanol--urea soluble and hot alkali soluble fractions were obtained, in addition to a hot alkali insoluble elastin residue from each sample. Variation in the protein composition of 23 samples from the lumenal surface of the severely atherosclerotic aorta of a 58-year-old human male were determined. The proteins soluble in the buffered-saline and the dodecyl sulfate-urea soluble polypeptides from each sample were analyzed by dodecyl sulfate--acrylamide gel electrophoresis. The amino acid compositions of the insoluble elastin fractions were determined. The 5 grossly normal intima samples had very similar gel electrophoresis band patterns and amino acid compositions. The 3 samples of necrotic gruel had markedly different dodecyl sulfate--urea soluble polypeptides than either normal or calcified tissue; they also had elastin fractions whose amino acid compositions were unique in that they contained 10 times more serine than elastin fractions from grossly normal intima. The 3 calcified samples had less saline or dodecyl sulfate soluble protein than either grossly normal or necrotic gruel samples, and had very altered elastin fraction compositions characterized by much higher contents of hydroxylysine than grossly normal intima. The elastin fractions of necrotic gruel and calcified tissue samples had little or no isodesmosine or desmosine, suggesting that little of the elastin found in healthy aorta tissue was present.
Atherosclerosis 1977 Feb
PMID:Variation in proteins of single lesions from the intima of the aorta from a human patient with severe atherosclerosis. 83 51

We studied the effect of heparin on proteoglycan synthesis by bovine aortic smooth muscle cells in culture. Confluent, growth-arrested cells were incubated with [35S]sulfate, [3H]glucosamine or [3]serine in the presence of 0-600 micrograms/ml heparin. Metabolically labeled proteoglycans secreted into the culture medium and associated with the cell layer were analyzed. In cultures treated with heparin there was a dose-dependent increase in [35S]sulfate incorporation into secreted proteoglycans which reached a maximum (35% above controls) at 100 micrograms/ml heparin. At higher concentrations of heparin, the stimulatory activity declined and finally disappeared. Radioactivity in cell-associated proteoglycans increased significantly (16% above controls) only in cultures treated with 100 micrograms/ml heparin. Heparin also produced similar increases in the incorporation of [3H]glucosamine and [3H]serine into secreted and cell-associated proteoglycans. While chondroitin sulfate, dermatan sulfate and heparan sulfate were elevated in the media, only chondroitin sulfate and heparan sulfate were increased in the cell layer. Heparin did not alter the degradation of proteoglycans. Heparin, while inhibiting the proliferation of subconfluent smooth muscle cells, also stimulated to a greater extent the incorporation of [35S]sulfate into proteoglycans. Other glycosaminoglycans, such as heparan sulfate, dermatan sulfate, heparin hexasaccharide and Sulodexide caused a significant but lesser stimulation of proteoglycan synthesis, while chondroitin sulfates and hyaluronic acid had no effect. Gel filtration chromatography of proteoglycans and their constituent glycosaminoglycans from heparin-treated and untreated cultures showed no differences in their molecular size. The results indicate that heparin can stimulate proteoglycan synthesis by vascular smooth muscle cells irrespective of their state of proliferation. This might have implications in vessel wall repair and arterial wall lipid deposition.
Atherosclerosis 1992 Jun
PMID:Heparin stimulates proteoglycan synthesis by vascular smooth muscle cells while suppressing cellular proliferation. 163 67

Proteoglycans (PG) produced by [35S]sulfate and [3H]serine labeled cultures of cholesterol-enriched macrophages obtained from atherosclerosis-susceptible White Carneau (WC) and -resistant Show Racer (SR) pigeons were characterized and assessed for their capacity to bind low density lipoprotein (LDL). The majority of 35S-labeled PG was released into the culture media in both WC and SR macrophage cultures and consisted of large and small size PG as determined by Sepharose CL-4B chromatography. Large PG were identified as chondroitin sulfate-PG comprised of 4-sulfated disaccharides whereas small PG consisted of primarily 4-sulfated chondroitin sulfate-PG and lesser amounts of heparin sulfate-PG. Experiments demonstrated that 32-34% of 35S-labeled large PG and 86-93% of small PG bound to LDL-substituted Sepharose. Interactions between PG and LDL-substituted Sepharose were inhibited in the presence of heparin or soluble LDL. Glycosaminoglycans derived from macrophage PG had a decreased binding affinity demonstrating the importance of an intact PG. The results suggest that macrophage PG may facilitate trapping of LDL in the intimal intima and promote foam cell formation through a mechanism involving the uptake of PG-LDL complexes.
Atherosclerosis 1991 Dec
PMID:Proteoglycans produced by cholesterol-enriched macrophages bind plasma low density lipoprotein. 178 5

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

The plasma concentration of lipoprotein (a) (Lp(a] varies widely in humans, and elevated concentrations of this lipoprotein are correlated with progression of atherosclerosis. Structural studies of Lp(a) have revealed that it is a low density lipoprotein (LDL)-like particle containing a unique glycoprotein, apo(a), which shares extensive homology with plasminogen. The apo(a) portion of Lp(a) binds to the carboxy-terminal heparin-binding domain of fibronectin. Incubation of Lp(a) or isolated apo(a) with fibronectin results in proteolytic cleavage of fibronectin which is, as visualized by gel electrophoresis and immunoblotting, distinct from that caused by plasmin or kallikrein. The proteolytic activity of apo(a) is of serine proteinase-type and displays specificity for arginine rather than lysine bonds. The molecular mechanism(s) underlying the association between Lp(a) and atherosclerosis remains an enigma.
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PMID:Interaction of lipoprotein(a) with fibronectin and its potential role in atherogenesis. 214 25

Sphingomyelin is found in plasma membranes and related organelles (such as endocytic vesicles and lysosomes) of all tissues, as well as in lipoproteins. Abnormalities in sphingomyelin metabolism have been associated with atherosclerosis, cancer and genetically transmitted diseases; however, except for Niemann-Pick disease, little is known about the mechanism for these disorders. Sphingomyelin biosynthesis de novo involves ceramide formation from serine and two mol of fatty acyl-CoA followed by addition of the phosphocholine headgroup. The headgroup appears to come from phosphatidylcholine, but other sources have not been ruled out. Factors that influence the rate of sphingomyelin synthesis include the availability of serine and palmitic acid, plus the relative activities of key enzymes of this pathway. Sphingomyelin turnover involves removal of the headgroup and amide-linked fatty acid by sphingomyelinases and ceramidases, respectively, which have been found in both lysosomes (with acidic pH optima) and plasma membranes (with neutral to alkaline pH optima). The enzymes of sphingomyelin turnover release ceramide and free sphingosine from endogenous substrates, which may have implications for the participation of a sphingomyelin/sphingosine cycle as another 'lipid second messenger' system.
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PMID:An update of the enzymology and regulation of sphingomyelin metabolism. 218 37

Cultured fibroblasts from patients with familial hyperapobetalipoproteinemia (hyperapoB) were used to determine if a defect in lipid metabolism was present. Three basic proteins (BP I, BP II, and BP III) were isolated from normal human serum by preparative isoelectric focusing, preparative SDS/PAGE, and reversed-phase HPLC. The Mr and pI values of these proteins were 14,000 and 9.10 for BP I, 27,500 and 8.48 for BP II, and 55,000 and 8.73 for BP III. These proteins differed significantly in their content of arginine, cysteine, proline, histidine, serine, and methionine. BP I appears to be the same protein as acylation-stimulating protein, but BP II and BP III appeared different from acylation-stimulating protein and other lipid carrier proteins. BP I, BP II, and BP III stimulated the incorporation of [14C]oleate into lipid esters in normal fibroblasts, an effect that was time and concentration dependent. In hyperapoB cells, BP II markedly increased (up to 9-fold) the incorporation of [14C]oleate into cholesteryl ester compared with that in normal cells; in addition, there was a 50% decrease in the stimulation of triglyceride acylation and cholesterol esterification with BP I. No difference between normal and hyperapoB cells was observed with BP III. In summary, the identification of another serum basic protein, BP II, led to the elucidation of another cellular defect in hyperapoB fibroblasts, enhanced cholesterol esterification, which may be related to the precocious atherosclerosis and abnormal lipoprotein metabolism seen in hyperapoB.
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PMID:Acylation-stimulatory activity in hyperapobetalipoproteinemic fibroblasts: enhanced cholesterol esterification with another serum basic protein, BP II. 224 73


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