Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty human aortas with varying degrees of atheroma graded macroscopically according to the WHO classification were taken at autopsy from subjects of different ages (24-86 years). Study by light microscopy showed aortas with an intact wall (4 subjects, 25-46 years) with a thin intima and regular elastic layers, and aortas with varying degrees of modification of the wall, where the intima was of varying thickness and the elastic fibers showed varying degrees of damage (moderate lesions: 5 subjects, 35-52 yrs; severe lesions: 21 subjects, 26-86 yrs). From each aorta, a 4-cm segment from the tunica media, free of atheromatous lesions, was defatted and subjected to successive treatment with EDTA-Tris, 6 M guanidine-HCl-Tris, 6 M guanidine-HCl-Tris-DTE and collagenase. The residues (EP residues) were subjected to amino acid (AA) analysis and transmission electron microscopy (TEM) study. In the young subject, the AA composition was similar to that of elastin and the TEM images were characteristic of this substance. In the aging subject, an increase in polar AA and a parallel decrease in apolar AA and crosslinks was noted. By TEM, the elastin was seen to be associated with abundant fibrillar material. Trypsin treatment of EP residues gave E residues, whose composition and TEM appearance were similar in all samples, corresponding to the standard composition of elastin and its classic appearance by electron microscopy. We suggest that the fibrillar material removed by trypsin is the morphological reflection of the chemical variations observed in the EP residues. These correspond to contamination of the elastin by a polar protein fraction. This contamination is closely correlated with age but not with the degree of atheroma. Thus the age-related chemical changes in elastin appear to be independent of the onset and evolution of atheromatous lesions. The 10-15 nm diameter of the contaminating fibrillar material suggests that may be the microfibrillar fraction of elastic tissue.
Atherosclerosis 1990 Jan
PMID:Age-related changes in the elastic tissue of the human thoracic aorta. 217 15

The sensitive and reliable dinitrophenyl (DNP) hapten sandwich staining (DHSS) procedure (B. Jasani et al., Virchows Arch (Pathol. Anat.), 406 (1985) 441-448) was used to study the distribution of immunoperoxidase staining seen with antibodies to seven protein markers in post-mortem heart tissue. This was obtained from 12 cases with macroscopic myocardial infarction and 17 cases without myocardial infarction (10 with and 7 without significant coronary artery atherosclerosis). The immunostaining patterns were compared with the appearances seen in adjacent sections stained by the routine haematoxylin and eosin (H & E) and phosphotungstic acid haematoxylin (PTAH) methods and a method previously recommended for the detection of early myocardial infarction, the haematoxylin basic fuchsin picric acid (HBFP) stain. Loss of immunostaining with an antibody to myoglobin was found to be a reliable and more objective marker of both early and established myocardial infarction compared with the histological stains. Antibodies to myosin, caeruloplasmin, C-reactive protein and pre-albumin gave similar but less reliable results, whilst those to complement factor C3b and alpha-1 anti-trypsin gave the least reliable results for early myocardial ischaemic/hypoxic damage. The immunocytochemical results are considered sufficiently encouraging to extend the work to a large number of sudden death cases in order to establish a new, more reliable approach to the detection of histologically latent ischaemic/hypoxic damage in the myocardium.
 ...
PMID:Immunocytochemical diagnosis of early myocardial ischaemic/hypoxic damage. 264 26

Plasma lipid transfer proteins stimulate transfer and molecular exchange of cholesteryl esters, phospholipids and triglycerides between individual plasma lipoproteins. To assess whether transfer protein activities are influenced by the inherent absence of apo B-containing lipoproteins, we determined cholesteryl ester and triglyceride transfer activities in the plasma of patients with abetalipoproteinemia (ABL). Transfer activities were measured in plasma fractions of d greater than 1.21 g/ml in 2 patients with abetalipoproteinemia and 12 normal volunteers and were expressed as a percent transfer of labeled lipid from donor high density lipoproteins to acceptor very low density lipoproteins. Cholesteryl ester and triglyceride transfer activities were reduced respectively by 50% and 66% in the plasma of patients with ABL. The addition of the plasma fraction d greater than 1.21 g/ml proteins from abetalipoproteinemic subjects resulted in progressive decreases in cholesteryl ester and triglyceride transfer activities. The reduced activities of these transfer proteins may reflect (at least in part) the presence of an inhibitor(s) which is heat-stable and trypsin-sensitive.
Atherosclerosis 1988 May
PMID:Neutral lipid transfer activities in the plasma of patients with abetalipoproteinemia. 337 77

Apolipoprotein(a) [apo(a)] is a glycoprotein with Mr approximately equal to 280,000 that is disulfide linked to apolipoprotein B in lipoprotein(a) particles. Elevated plasma levels of lipoprotein(a) are correlated with atherosclerosis. Partial amino acid sequence of apo(a) shows that it has striking homology to plasminogen. Plasminogen is a plasma serine protease zymogen that consists of five homologous and tandemly repeated domains called kringles and a trypsin-like protease domain. The amino-terminal sequence obtained for apo(a) is homologous to the beginning of kringle 4 but not the amino terminus of plasminogen. Apo(a) was subjected to limited proteolysis by trypsin or V8 protease, and fragments generated were isolated and sequenced. Sequences obtained from several of these fragments are highly (77-100%) homologous to plasminogen residues 391-421, which reside within kringle 4. Analysis of these internal apo(a) sequences revealed that apo(a) may contain at least two kringle 4-like domains. A sequence obtained from another tryptic fragment also shows homology to the end of kringle 4 and the beginning of kringle 5. Sequence data obtained from two tryptic fragments show homology with the protease domain of plasminogen. One of these sequences is homologous to the sequences surrounding the activation site of plasminogen. Plasminogen is activated by the cleavage of a specific arginine residue by urokinase and tissue plasminogen activator; however, the corresponding site in apo(a) is a serine that would not be cleaved by tissue plasminogen activator or urokinase. Using a plasmin-specific assay, no proteolytic activity could be demonstrated for lipoprotein(a) particles. These results suggest that apo(a) contains kringle-like domains and an inactive protease domain.
 ...
PMID:Partial amino acid sequence of apolipoprotein(a) shows that it is homologous to plasminogen. 347 6

The interaction between HDL and macrophages in culture was studied using HDL labeled with 125I and with [3H]cholesteryl linoleyl ether. Mouse peritoneal macrophages and the macrophage-like cell lines J-774 and CT2, of mouse origin, took up and metabolized rat HDL and human HDL3. In all 3 cell types using both rat and human HDL, the uptake of the cholesteryl ester moiety as measured with the nondegradable cholesteryl ether analog, was 2-5-fold higher when compared to the protein moiety. Modulation of the cholesterol content of the cultured macrophages affected the uptake of both protein and lipid moieties of HDL to the same extent. When the macrophages had interacted with the labeled HDL for 5 h and were post-incubated for 20 h, the amount of [125I]HDL which reappeared in the post incubation medium was twice that of [3H]cholesteryl linoleyl ether-HDL. The site from which the HDL may have returned to the culture medium was tentatively localized to the trypsin-releasable, cell surface-related compartment. The present results indicate that interaction between macrophages and HDL may result in some loss of cholesteryl ester and possibly render the particle more receptive for cellular cholesterol removal.
Atherosclerosis 1987 May
PMID:Preferential uptake of cholesteryl ester-HDL by cultured macrophages. 360 29

The effect of human arterial proteoglycans (PG1) on the interaction of low density lipoprotein (LDL) with cultured human monocyte-derived macrophages (HMDM) was studied. LDL was insolubilized by treatment with chondroitin-6-sulfate-rich, partially purified PG1. The LDL, resolubilized in culture medium, was added to HMDM. The PG1 pretreated LDL induced lipid accumulation in the HMDM, converting them into foam cells. Mass determination of lipids by spectrophotometric and chromatographic procedures showed a 2-4-fold accumulation of triglycerides, phospholipids, unesterified cholesterol and cholesterol esters in 48 h, in the HMDM incubated with PG pretreated LDL, when compared to those incubated with native LDL. Incorporation of [14C]oleic acid into the HMDM lipid esters correlated with the accumulation. Association of 125I-labeled LDL and of fluorescent labeled LDL (3,3-octadecyl indocarbocyanine) to HMDM also indicated that the PG1-pretreatment of LDL increased its uptake. Density gradient centrifugation, isoelectric focusing and electron microscopy showed that, when added to the cells, the PG1 pretreated LDL was not aggregated or altered in its surface charge. However, controlled trypsin treatment and polypeptide pattern analysis indicate that the accessibility of apoB has been altered. The results suggest that changes in the surface of LDL, induced by the arterial PG1, lead to increased endocytosis of the lipoprotein and stimulation of lipid synthesis in the macrophages. The possibility that a similar process may cause lipid accumulation in arterial macrophages is discussed.
Atherosclerosis 1987 Oct
PMID:Effect of arterial proteoglycans on the interaction of LDL with human monocyte-derived macrophages. 367 9

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

Collagen secretion stimulating activity (CSSA) of bovine arterial smooth muscle cells (SMC) was released to the culture medium after injury of cultured SMC by dimethylsulphoxide-soluble particles from cigarette smoke, but not from uninjured cells. Total protein secretion and DNA synthesis were not stimulated in new SMC by the conditioned medium containing the CSSA. The presence of protease inhibitors before assay did not influence CSSA, but this activity was completely abolished if protease inhibitors were present before injury was induced. The sensitivity to trypsin and heat suggested a protein nature of the activity. CSSA exhibited marked charge and size heterogeneity when subjected to ion exchange and gel chromatographies, and the fraction procedures revealed CSSA peaks with approximate molecular weights greater than 1.5 X 10(6), 450 000, 250 000, 15 000 and less than 10 000, respectively. No CSSA peaks were seen when conditioned medium from uninjured cells was used. It is concluded that SMC injured by dimethylsulphoxide extractable material from cigarette smoke release protein(s) stimulating secretion of newly synthesized collagen, but not of total protein and DNA synthesis, in new SMC cultures.
Atherosclerosis 1986 Feb
PMID:Stimulation of collagen secretion by factors released from injured arterial smooth muscle cells in culture. 396 44

Rabbit and bovine arterial smooth muscle cells (SMC) and human skin fibroblasts were lysed by freezing and thawing in the presence of protease inhibitors (PI). The supernatant was assayed for growth stimulating activity (GSA), and it stimulated the growth of SMC and fibroblasts, but not human and bovine endothelial cells. GSA was sensitive to heat and trypsin treatment, stimulated DNA synthesis after a lag time of 12-15 hours, and exhibited marked size and charge heterogeneity when subjected to gel chromatographies. GSA differed from many other known growth factors, mainly platelet derived growth factor (PDGF), through the behavior on ion exchange chromatography, the heat sensitivity and the lack of decline in activity in the presence of anti PDGF antibodies. The data suggests that several growth stimulating proteins can be obtained through the lysis of SMC or fibroblasts with possible implications for atherosclerosis and wound healing.
 ...
PMID:Growth stimulating activity from lysed cultured arterial smooth muscle cells and skin fibroblasts. 409 82

Bovine medial explants in culture synthesize a potent inhibitor of mammalian collagenase but not of bacterial collagenase. This inhibitor has been partially purified and has an apparent molecular weight of 45,000. It is a glycoprotein and is stable to heat, trypsin, acid and mercurials. Inhibitory activity is destroyed on reductive alkylation. The inhibitor interacts with collagenase and this interaction leads to the loss of enzymatic activity. This inhibitor may play a physiological role in the control of collagen degradation in blood vessels.
Atherosclerosis 1980 Jan
PMID:Purification and properties of a collagenase inhibitor from cultures of bovine aorta. 624 63


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>