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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cellular origin and development of radiation-induced atheromatous plaques in the carotid artery of the hypercholesterolemic rabbit have been studied morphologically from a few hours post-irradiation up to several weeks later. As early as 8 h following local X-irradiation (500 or 1,000 rad) mononuclear cells, presumably blood monocytes, enter the subendothelial space. The cells have disappeared again 10 days post-irradiation in normocholesterolemic animals. In irradiated hypercholesterolemic animals, however, the invading mononuclear cells transform into lipophages and become so-called foam cells, visible from the second day post-irradiation. The number of lipophages increases with time resulting in plaques of about 5-10 cell layers after 20 days. From 20 days post-irradiation onwards smooth muscle cells enter the plaque by migrating from the tunica media through the fenestrations of the lamina elastica interna. Smooth muscle cells are found to contain less lipid vacuoles than monocyte-derived lipophages. At 30 days post-irradiation the smooth muscle cells have formed parallel layers in the luminal side of the plaque encapsulating an inner core of foam cells and other material. The morphology of the plaque at 30 days post-irradiation is similar to that reported for advanced plaques developing in rabbits by mere cholesterol feeding over a relatively long period. In irradiated normocholesterolemic and in non-irradiated hypercholesterolemic rabbits plaques are not observed in the carotid arteries during the experimental period. The early involvement of blood monocytes has been separated from the later role of medial smooth muscle cells in radiation-induced plaque formation. The results suggest that the underlying process in this lesion may be understood in terms of a sterile inflammation, complicated by an immediate fatty degeneration and followed by repair phenomena. The combination of hypercholesterolemia and ionizing radiation may serve as a useful experimental model for further studies in various animal species on why and how plaques originate, develop or regress and how they could possibly be prevented. The relevance of the results to radiotherapy in humans is mentioned briefly.
Virchows Arch B Cell Pathol Incl Mol Pathol 1983
PMID:On the cellular origin and development of atheromatous plaques. A light and electron microscopic study of combined X-ray and hypercholesterolemia-induced atheromatosis in the carotid artery of the rabbit. 613 15

Quantitative cytochemical and microfluorimetric techniques were employed to compare mural intermediary metabolism--endothelial macromolecular uptake changes in spontaneous aortic-arteriosclerotic lesions of normolipemic New Zealand White rabbits. Specifically, mural succinic (SDH), lactic (LDH), and glucose-6-phosphate (G-6-PDH) dehydrogenase activities and luminal surface uptake of fluorescein isothiocyanate-conjugated bovine serum albumin (FITC-BSA) were measured in lesion sites abnormally resistant (calcified) and susceptible (proliferative) to dietary hypercholesterolemia. Calcified lesions exhibited severe (55-66%) diminution of SDH, LDH, and G-6-PDH activities within the involved inner mural zone and a comparable (68%) decline in luminal FITC-BSA uptake. Concomitant reductions in FITC-BSA uptake (30%) and marker enzymes of the predominant energy transducing pathways in arterial tissue, i.e., SDH (30%) and LDH (31%), were evidenced in proliferative foci, whereas G-6-PDH was augmented (52%) in comparison to nonlesioned aortic segments. These data lend additional support to the concept that endothelial uptake of plasma-borne macromolecules is coupled to oxidizable substrate requirements of inner avascular compartments of the arterial wall. It is postulated that diminished macromolecular transport in these degenerative lesions stems from reduced mural metabolic demands, and that pharmacologic reduction of vascular smooth muscle metabolism may depress uptake of sclerogenic macromolecules.
Exp Mol Pathol 1984 Feb
PMID:Cytochemical correlates of atherosclerosis-resistant and susceptible lesions of the normal rabbit aorta. 669 4

The activities of superoxide dismutase (SOD, EC 1.15.1.1), glutathione peroxidase (GPx, EC 1.11.1.9) and the levels of alpha-tocopherol and oxidized lipoproteins were investigated in the plasma of New Zealand rabbits either before or after cholesterol-diet induced hypercholesterolemia. Plasma SOD activity increased while GPx activity decreased after 60 days of cholesterol feeding. However, in the cholesterol-fed rabbits the release of superoxide dismutase fraction C from vasculature by heparin was lower than that in control rabbits. The levels of triglyceride hydroperoxides increased in low density and high density lipoproteins after feeding rabbits with the cholesterol-rich diet during 60 days. Also, a trend for increasing cholesteryl ester hydroperoxides was observed in beta-very low density and high density lipoproteins. An increase in alpha-tocopherol concentration (microM) was observed in very low density and low density lipoprotein fractions, but after normalization of these results to the cholesterol content of lipoprotein particles only the alpha-tocopherol content of low density lipoprotein remained higher after 60 days of cholesterol feeding. The data suggest that low glutathione peroxidase and superoxide dismutase fraction C activities may facilitate intravascular lipoprotein oxidation by oxidant species generated by the endothelium or blood cells.
Biochem Mol Biol Int 1995 Jul
PMID:Plasma antioxidant enzymes and oxidized lipoproteins in hypercholesterolemic rabbits. 754 68

Various matrices were reacted with four different activation reagents, in order to prepare immuno-adsorbents for the selective removal of low-density lipoproteins from blood plasma of patients affected by hypercholesterolaemia. The resulting immuno-adsorbents were compared to that obtained earlier with cyanogen bromide activation, in terms of coupling yield, adsorption capacity and moreover stability towards the various chemical and biochemical conditions to which they are submitted during their handling. Tresyl chloride-activated Sepharose 6 Fast Flow turns out to afford optimal stability in the whole pH range tested.
J Mol Recognit
PMID:Importance of the matrix and its chemical activation on the stability of immuno-adsorbents. 759 44

Familial defective apolipoprotein B-100 (FDB) is a dominantly-inherited genetic disorder causing primary hypercholesterolemia and premature coronary heart disease. To date, only two mutations causing FDB have been identified. A rapid non-radioactive technique is described to detect both disease-related apolipoprotein B point mutations in polymerase chain reaction (PCR) products amplified from genomic DNA. Heteroduplex formation between different alleles from FDB heterozygotes was shown to be visible directly after electrophoresis of PCR products and staining in low cross-linking polyacrylamide gels. We found that the simplicity of the method, in addition to its potential to identify new mutations in the amplified PCR product, makes heteroduplex detection the preferred initial method of screening potential heterozygotes.
Mol Cell Probes 1994 Dec
PMID:Detection of two point mutations causing familial defective apolipoprotein B-100 by heteroduplex analysis. 770 Feb 73

The biosynthetic pathway of the CoQ polyisoprenoid side chain, starting from acetyl-CoA and proceeding through mevalonate and isopentenylpyrophosphate, is the same as that of cholesterol. We performed this study to evaluate whether vastatins (hypocholesterolemic drugs that inhibit HMG-CoA reductase) modify blood levels of ubiquinone. Thirty-four unrelated outpatients with hypercholesterolemia (IIa phenotype) were treated with 20 mg of simvastatin for a 6-month period (group S) or with 20 mg of simvastatin plus 100 mg CoQ10 (group US). The following parameters were evaluated at time 0, 45, 90, 135 and 180 days: total plasma cholesterol (TC), HDL-cholesterol, LDL-cholesterol (LDL-C), triglycerides (TG), apo A1, apo B and CoQ10 in plasma and platelets. In the S group, there was a marked decrease in TC and LDL-C (from 290.3 mg/dl to 228.7 mg/dl for TC and from 228.7 mg/dl to 167.6 mg/dl for LDL-C) and in plasma CoQ10 levels from 1.08 mg/dl to 0.80 mg/dl. In contrast, in the US group we observed a significant increase of CoQ10 in plasma (from 1.20 to 1.48 mg/dl) while the hypocholesterolemic effect was similar to that observed in the S group. Platelet CoQ10 also decreased in the S group (from 104 to 90 ng/mg) and increased in the US group (from 95 to 145 ng/mg). This study demonstrates that simvastatin lowers both LDL-C and apo B plasma levels together with the plasma and platelet levels of CoQ10, and that CoQ10 therapy prevents both plasma and platelet CoQ10 decrease, without affecting the cholesterol lowering effect of simvastatin.
Mol Aspects Med 1994
PMID:Exogenous CoQ10 supplementation prevents plasma ubiquinone reduction induced by HMG-CoA reductase inhibitors. 775 30

A rapid detection of the Arg3500-->Gln mutation of human apolipoprotein B-100 is of particular interest because of its prevalence in familial forms of hypercholesterolemia. A simple procedure, based on amplification by polymerase chain reaction (PCR) and NlaIII endonuclease restriction cleavage, allows this diagnosis without ambiguity. By using two oligonucleotide primers carrying one mismatch each, two permanent restriction sites were generated in the normal allele, while one of them disappeared in the mutant allele. Thus, the two alleles can be differentiated by their specific N/aIII restriction profile.
Mol Cell Probes 1994 Jun
PMID:Application of PCR site-directed mutagenesis for a rapid and accurate detection of mutation 3500 (Arg-->Gln) of human apolipoprotein B-100. 796 2

We have studied the expression of apolipoprotein E (ApoE) mRNA in the cerebella of control and experimental rabbits fed with a cholesterol-rich diet for 8 weeks. Cholesterol-treated rabbits show a dramatic increase in serum cholesterol levels; however, no significant variations in the expression level of cerebellar ApoE mRNA were found in comparison to control rabbits. In addition, no differences were observed between control and hypercholesterolemic rabbits in the in situ hybridization pattern of ApoE mRNA on cerebellar cortex sections. ApoE mRNA was localized in astroglial processes associated with Purkinje cell bodies and dendrites, granule cell clusters, blood vessels and nerve fibers of the white matter. No expression of ApoE mRNA was observed in Purkinje and granule cell neurons. Polarized light examination of cryostat cerebellar sections revealed the absence of cholesterol-rich microglia/macrophage cells induced by the hypercholesterolemia. In this way, neither reactive microglial cells nor perivascular phagocytes were found by ultrastructural analysis in hypercholesterolemic conditions. The pattern of glial fibrillary acidic protein of the astroglial cells of the cerebellar cortex as well as their nuclear size were unchanged following cholesterol treatment, indicating the absence of astroglial activation induced by hypercholesterolemia. Our results suggest that cerebellar ApoE does not contribute to the general cholesterol homeostasis outside of the brain and supports the view that this cerebellar ApoE is involved in paracrine and autocrine functions particularly related with synapse turnover and membrane remodelling of astroglial cells.
Brain Res Mol Brain Res 1994 Jan
PMID:Apolipoprotein E expression in the cerebellum of normal and hypercholesterolemic rabbits. 816 12

Inbred mouse strains vary in susceptibility or resistance to dietary induced atherosclerosis. To investigate the effect of polyunsaturated fat feeding on postprandial serum cholesterol levels, in C57BL/67 (B6) and BALB/cJ inbred mice, we fed by stomach gavage previously fasted mice, a mixture containing 30% sunflower oil, 5% cholesterol, 2% sodium cholate and 0.5% choline chloride. The most significant difference in serum cholesterol levels between B6 and BALB/cJ mouse strains was observed at 2 h postfeeding. Susceptible B6 strain mice had a 41% postprandial increment in serum cholesterol. The resistant BALB/cJ strain had an insignificant 16% rise in serum cholesterol, at 2 h. We next examined eight other inbred mouse strains, to identify the gene(s) that regulate the observed 2 h postprandial hypercholesterolemia response, in the susceptible B6 mouse strain. Only the C57BR/cdJ and C57L/J strains developed postprandial hypercholesterolemia, at 2 h. The C57BR/cdJ strain had a 20% increase and the C57L/J strain a 62% increase in postprandial serum cholesterol levels. From this result, we found that the postprandial hypercholesterolemic response to an acute polyunsaturated fat-cholesterol feed, cosegregated with the a allele at the Gpd-1 and Ahd-1 loci, on mouse chromosome 4. In this study, non-responsiveness cosegregated with the b allele at the Gpd-1 and Ahd-1 loci. Thus polyunsaturated fat-cholesterol induced postprandial hypercholesterolemia appeared to be genetically determined by a gene located between the Gpd-1 and Ahd-1 loci, in mice. The putative gene regulating polyunsaturated fat-cholesterol induced post-absorptive hypercholesterolemia was designated Phc-2.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem 1994 Jan 12
PMID:Regulation of polyunsaturated fat induced postprandial hypercholesterolemia by a novel gene Phc-2. 819 Jan 22

The effects of hypercholesterolemia on both the initial and chronic phases of rat nephrotoxic serum (NTS) nephritis have been investigated. Injury during the initial phase of NTS nephritis in hypercholesterolemic rats maintained on a cholesterol-supplemented diet (Group 2) was characterized by segmentally accentuated accumulations of vacuolated cells with lipid droplets (foam cells) in the glomeruli, while the kidneys of rats fed a standard diet (Group 1) revealed only mild intracapillary cell proliferation. Immunoelectron microscopy showed that the foam cells observed in Group 2 rats were largely derived from macrophages. The glomerular macrophage number, defined by the number of ED1-positive cells per glomerulus, was significantly higher in Group 2 than in Group 1 animals at days 5-6 (3.4 +/- 1.4 in Group 1 against 6.3 +/- 1.0 in Group 2; p < 0.01) as well as at days 21-28 (5.5 +/- 2.6 in Group 1 against 10.9 +/- 2.8 in Group 2; p < 0.01). In contrast, the numbers of OX19-positive T-lymphocytes and OX33-positive B-lymphocytes were similar in both groups. In the chronic phase of NTS nephritis at week 20, semiquantitative evaluation of the glomerular lesions disclosed more severe focal segmental glomerulosclerosis (FSGS) in Group 2 compared with Group 1 animals (glomerular injury score: 14 +/- 10 in Group 1 against 73 +/- 17 in Group 2; p < 0.01). Accumulations of lipid and foam cells were invariably seen in the sclerotic foci of Group 2 animals. The results indicate that hypercholesterolemia played an important role in the accelerated development of FSGS in rat NTS nephritis.(ABSTRACT TRUNCATED AT 250 WORDS)
Virchows Arch B Cell Pathol Incl Mol Pathol 1993
PMID:Effects of hypercholesterolemia on initial and chronic phases of rat nephrotoxic serum nephritis: development of focal segmental glomerulosclerosis, analogous to atherosclerosis. 822 Aug 24


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