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)

Serial liver biopsies were carried out in 67 patients with HLP and/or fatty liver before, during short- and long-term therapy with CPIB and after termination of therapy. Results (1) Decrease of liver glycogen from 4.17% to 2.69% (wet weight, P less than 0.02). (2) Insignificant changes of liver triglyceride content. (3) Significant decrease of manganese, while the concentrations of zinc and copper in the liver biopsy specimens remained unchanged. (4) No signs of liver intoxication or cancerogeneous effects of light-microscopic pictures. (5) Significant increases in numbers of mitochondria and cristae as well as a hypertrophy of endoplasmic reticulum with longer lasting therapy. (6) Striking focal proliferation of cristae mitochondriales in 3 cases on longterm treatment. (7) Regression of the mitochondrial alterations after termination of the CPIB therapy. Our findings suggest that an increased number of mitochondria and of their inner membranes in the liver cells induced by CPIB could play an important role in the hypolipidemic action of the drug.
Atherosclerosis 1980 Jun
PMID:Effects of p-chlorophenoxyisobutyric acid (CPIB) on the human liver. 740 47

When experimental animals are kept on an atherogenic diet the NADP.H-dependent phospholipid deoxygenase in the membranes of the hepatic endoplasmic reticulum is activated and the degree of membrane oxidation is increased. "Peroxide" modification of microsomal membranes is attended by changes in their conformation and as a consequence, changes in the activity of membrane-bound enzymes. Proceeding from the fact that the synthesis of the components and the assembly of the supramolecular lipoprotein structure as well as cholesterol catabolism are accomplished by the enzyme systems localized in the hepatic microsomes, the role of peroxidation of the microsomal lipids in the pathogenesis of atherosclerosis is discussed.
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PMID:[Lipid peroxides and atherosclerosis. Hypothesis: the role of cholesterol and free-radical lipid peroxidation in altering cell membrane properties in hypercholesterolemia and atherosclerosis]. 741 95

Specimens of ductus arteriosus and venosus from 2-month-old and 6-month-old swine were examined by electron microscope. The purpose of the study was to observe the effects of vessel closure and hypoxia on medial vascular smooth muscle cells. At 6 months of age, smooth muscle cells from the medial layer of ductus arteriosus showed signs of considerable cellular degeneration and contained lipid vacuoles which were often surrounded by granular endoplasmic reticulum. Specimens from the portal side of ductus venosus showed initial stages of smooth muscle cell degeneration and lipid vacuolization, while samples from the hepatic side of ductus venosus were nearly normal. This study contains the first reported morphological evidence of organelles in vascular smooth muscle cells which are responsible for endogenous lipid droplet production.
Atherosclerosis 1980 Oct
PMID:Morphological evidence of endogenous lipid production in swine ductus vasculature. 742 6

Apo A-I, the major protein component of high density lipoprotein (HDL), is synthesized by hepatic and intestinal cells and assembled with lipids to produce, in as yet incompletely understood ways, a mature HDL particle. For many secreted proteins only a portion of newly synthesized polypeptides are secreted, with the remainder being degraded at intracellular sites. For example apolipoprotein B secretion is controlled by the extent of intracellular degradation of the protein. Here we have systematically examined whether there is significant intracellular degradation of nascent apo A-I. We find that in two hepatic cell types, primary cultures of hepatocytes from cynomolgus monkey and HepG2 hepatocarcinoma cells, essentially all apo A-I that is synthesized is eventually secreted. A non-hepatic cell line, Chinese hamster ovary cells transfected with the apo A-I gene, secreted somewhat less (65%) of the apo A-I synthesized. In a careful kinetic analysis, the rate of apo A-I secretion was found to be identical between the three cell types. This indicates that the mechanisms governing secretion are conserved among the different cell types. Further, the rate of secretion was the same for apo A-I in a lipid-poor form and in a form found associated in the medium with sufficient lipid to promote flotation in density gradients. The kinetic analysis indicates that there are two rate limiting steps to apo A-I secretion from the cell. It has previously been suggested that, for most proteins, exit from the endoplasmic reticulum is the rate limiting step in the secretory pathway.(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1994 Apr
PMID:The efficiency and kinetics of secretion of apolipoprotein A-I in hepatic and non-hepatic cells. 806 Mar 82

Hyperlipidemia arises from a disturbance in the balance between production and degradation of lipoprotein particles. Variation in the secretion of human apolipoprotein B (apoB), the major protein component of triglyceride-rich lipoproteins, directly affects this homeostasis. Naturally occurring apoB signal peptide variants (associated with hypertriglyceridemia, altered postprandial lipid metabolism, or atherosclerosis) were investigated for their ability to direct transit through the secretion pathway. Three apoB signal peptide isoforms were fused to the secretory protein, invertase, and expressed in yeast. A deletion or insertion in the hydrophobic core of the signal peptide mediated inefficient translocation into the endoplasmic reticulum and was secretion-defective, relative to the common 27-residue isoform. Additionally, the insertion apoB isoform was observed in yeast to confer a defect in export from the endoplasmic reticulum. Secretion of the apoB signal peptide-invertase fusions responded positively to an inhibitor of calpain type I proteases. These observations suggest that the apoB signal peptide plays a role in determining the levels of apoB degradation and secretion and, thus, hyperlipidemia.
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PMID:Human apolipoprotein B signal sequence variants confer a secretion-defective phenotype when expressed in yeast. 806 10

Seven cases of inflammatory abdominal aortic aneurysms (IAs) were studied by light microscopy, transmission electron microscopy (TEM) and immunohistochemistry. Microscopically, atherosclerosis coexisted with adventitial fibrosis and inflammation. The inflammatory component showed a follicular and a diffuse pattern. Fibrous entrapment of fatty tissue, adventitial vasculitis, neuritis were also common findings. By TEM, sparse smooth muscle cells having dilated cisternae of rough endoplasmic reticulum, large bundles of collagen fibres and oedematous, amorphous fibrillary elastin were observed. By immunohistochemistry, the follicles mostly contained CD22+ B-cells. T4- (CD2+/CD4+/CD8-), T8-(CD2+/CD4-/CD8+) cells as well as macrophages (CD4+/CD11c+) and follicular dendritic reticulum cells (DRC1+) were also detected. The monoclonal antibody Ki-67 reacted with 2-48% of germinal center cells. In the fibrous extrafollicular adventitia, actively synthesizing plasma cells prevailed over T4-cells, and macrophages. Some of the macrophages were also activated (CD4+/CD11c+/CD25+/CD30-). IgM, IgG and C3c deposits were detected in the fibrous zone, in the germinal centers, within adventitial vessels and nerves. HLA-DR antigen was diffusely expressed in cells populating both the fibrous and the follicular zones as well as in endothelial and Schwann cells. These findings suggest that IAs could develop in some individuals affected by advanced atherosclerosis of the abdominal aorta through a pathogenic B-cell response to locally presented antigens.
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PMID:An immunohistochemical study of inflammatory abdominal aortic aneurysms. 809 31

Intimal thickening in human arteries is considered as a site of predilection for atherosclerosis. The placement of a flexible, physically nonconstrictive, silicone cuff around the rabbit carotid artery induced a neointima composed of smooth muscle cells (SMCs) within 14 days. To investigate possible alterations of the endothelial cells (ECs) during neointima formation, their morphology was examined with scanning electron microscopy (SEM), transmission electron microscopy (TEM), and confocal microscopy. In the early postoperative period (6 hours), both cuffed and sham-operated arteries demonstrated small foci (5 to 200 microns) of denudation, presumably as a consequence of the manipulation. Within 24 hours the luminal surface of the cuffed and sham-operated arteries was completely covered with endothelium, which remained continuous throughout the study. However, after 1 week the ECs of the cuffed arteries contained a pronounced rough endoplasmic reticulum. From 6 hours until 3 days, polymorphonuclear leukocytes infiltrated the cuffed but not the sham-operated arteries from the lumen. Subendothelial SMC accumulation in the cuffed arteries began after this time period. At day 14 a full-blown neointima composed of longitudinally oriented SMCs had formed in the cuffed arteries. The sham-operated arteries did not develop a neointima. During neointima formation immunoreactivity for von Willebrand factor (vWf) increased in the ECs, and vWf was deposited in the extracellular spaces of the neointima. At day 14 the area of vWf deposits correlated positively with the area of the neointima (r = .73, P < .001). In subsequent weeks, the intimal area did not increase, and vWf deposits vanished from the neointimal matrix. The endothelium of the sham-operated arteries showed no change in vWf immunoreactivity compared with untreated arteries throughout the study. The altered ultrastructural morphology of the ECs and the concurrent vWf deposition in cuffed but not in sham-operated arteries point to alterations in EC function during the development of the neointima. The vWf secretion could possibly lead to increased adhesiveness of the extracellular matrix for the ECs as well as modulate neointima formation.
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PMID:The endothelium during cuff-induced neointima formation in the rabbit carotid artery. 824 Nov 10

In a search for early atherosclerotic lesions, we have investigated grossly normal areas of human thoracic aortas taken at autopsy from 40 trauma victims aged from 3 to 40 years. Two areas of aorta were compared: lesion predisposed to atherosclerosis (LP) area localized on the dorsal aspect of the vessel along the row of intercostal branching sites, and lesion resistant (LR) area located on the ventral aspect of the vessel. Accumulation of apolipoprotein B (apo B) was found in LP aortic area of each child older than 6 years. Similar retention of apo B in LR area appeared only in aortas of teenagers. The apo B staining increased with age in both areas tested but was usually of a greater extent in LP area than in LR area. Typical smooth muscle cells (SMCs) and a few monocytes/macrophages (Mn/Mph) were revealed in the intimal layer of all aortas examined. The number of Mn/Mph dramatically increased in LP areas of individuals over 17 years. Quantitative study of double stained sections has shown a 2- to 6-fold enhanced number of Mn/Mph in LP area compared with LR aortic area of 10 men over 21 years. Focal infiltration of Mn/Mph in aortas of young adults occurred without endothelial denudation. In addition, some intimal SMCs in LP area of 12 aortas out of 29 expressed desmin and contained well-developed endoplasmic reticulum, while such cells were seldom detected in LP area of the vessels. Thus, focal accumulation of apo B with subsequent Mn/Mph infiltration and SMC phenotypic modulation in LP aortic area of young adults may be causally involved in fatty streak and atherosclerotic plaque formation.
Atherosclerosis 1993 May
PMID:Monocyte/macrophage accumulation and smooth muscle cell phenotypes in early atherosclerotic lesions of human aorta. 835 56

Intracellular protein transport in endothelial cells is selectively inhibited by homocysteine, a thiol amino acid associated with both thrombosis and atherosclerosis. In a previous study, homocysteine decreased cell surface expression of the surface transmembrane glycoprotein thrombomodulin without decreasing secretion of another endothelial cell protein, plasminogen activator inhibitor-1. To define further the effects of homocysteine on protein transport, we examined the processing and secretion of the multimeric glycoprotein von Willebrand factor (vWF) in human umbilical vein endothelial cells. Incubation with 2 mmol/L homocysteine resulted in complete loss of vWF multimers and prevented asparagine-linked oligosaccharide maturation, propeptide cleavage, and secretion; these effects are consistent with impaired exit from the endoplasmic reticulum (ER). Dimerization was only partially inhibited, suggesting that homocysteine causes retention of provWF in the ER without preventing dimer formation. In pulse-chase incubations, intracellular provWF was degraded before exiting the ER in homocysteine-treated cells. Homocysteine also inhibited the processing and secretion of a carboxyl-terminal truncation mutant of human provWF expressed in rat insulinoma cells, indicating that retention in the endoplasmic reticulum can be mediated by regions of provWF apart from the carboxyl-terminal 20-Kd segment. These results suggest that retention of secretory proteins in the ER is regulated by redox mechanisms and imply that the intracellular transport of multiple endothelial cell proteins may be altered in patients with homocystinuria.
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PMID:Homocysteine inhibits von Willebrand factor processing and secretion by preventing transport from the endoplasmic reticulum. 842 60

Analysis of serial ultrathin sections of the human aortic intima detected a new cell yet to be described in the literature. These cells, which we have designated Vascular Dendritic Cells, appeared in contact with each other and with other intimal cells. Vascular dendiritic cells are characterised by ultrastructural features similar to those of dendritic cells, including a well developed smooth endoplasmic reticulum and the presence of several processes which were 3-5 or more times in excess of the size of the cell body. In areas of the normal aorta resistant to atherosclerosis, vascular dendritic cells were mainly localised in the subendothelial layer where they contacted both endothelial cells and smooth muscle cells. In areas of the normal aorta predisposed to atherosclerosis, vascular dendritic cells were distributed throughout the intima and the cellular interactions were altered with the vascular dendritic cells, developing multiple contacts with monocyte/macrophages and lymphocyte-like cells. Aortic areas predisposed to atherosclerosis showed the destruction of some vascular dendritic cell processes where they apposed endothelial cells. We speculate that vascular dendritic cells (VDCs) are a variety of dendritic cell and are involved in the maintenance of homeostasis in normal arterial intima. Vascular dendritic cells may be important in the development of atherosclerotic lesions, possibly through an immune mechanism.
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PMID:Ultrastructural recognition of cells with dendritic cell morphology in human aortic intima. Contacting interactions of Vascular Dendritic Cells in athero-resistant and athero-prone areas of the normal aorta. 852 38


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