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)

Foam cells, either myogenic or macrophagic, are commonly detected in experimental and human fibro-atheromatous plaques. Their role in human atherosclerosis is not yet understood. This paper reports on a preliminary autoradiographic study combined with ultrastructural observations in the human fibro-atheromatous plaque. Most of the autoradiographic silver grains appeared on foam cells and monocyte-like cells, thus suggesting a local proliferation of these cells.
Atherosclerosis 1983 Jul
PMID:Autoradiographic and ultrastructural studies on the human fibro-atheromatous plaque. 688 12

Wistar female rats were made hypertensive by applying a silver clip to the left renal artery and removing the right kidney. In aortas, the proliferation fraction of smooth muscle cells, DNA synthesis and wet weight have been correlated with the blood pressure increase subsequent to the operation. A wave of proliferation of smooth muscle cells in the aortic media is triggered immediately after the highest increased rate of blood pressure. When blood pressure stabilizes at high values, the metabolism of nucleic acid within the aortic media resumes its normal level but the arterial changes previously established persist. The sequence of pathological events responsible for these changes could be: increment of blood pressure; increase in wall stress; proliferation of smooth muscle cells; thickening of arterial wall; correction of the wall stress; end of proliferation. The consequence of this early proliferation of aortic smooth muscle cells is not clear but it is probably one of the mechanisms through which high blood pressure is sustained. It can also participate in atherogenesis, being in this way one of the bases of the well-known relationship between hypertension and atherosclerosis.
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PMID:Kinetics of proliferation of rat aortic smooth muscle cells in Goldblatt one-kidney, one-clip hypertension. 688 19

The luminal surface of the aorta and the carotid artery in normal and cholesterol-fed rabbits (3 weeks, 6 weeks, and 8 months of alimentary hypercholesterolemia) was studied by scanning electron microscopy (SEM). To study endothelial injury the vessels were perfused and stained under physiological pressure. The frequency of large and small endothelial defects was determined per surface unit of endothelium in the normal and experimental groups of rabbits. Loss of endothelial cells was regarded as a large defect, argyrophilic cells, craters, and stomata were regarded as small ones. It was found that the percentage of regions without endothelial cells was similar in both control rabbits and in rabbits with experimental atherosclerosis (0.005--0.04% of the total surface examined). The frequency of small endothelial defects increased in rabbits after 3 weeks of hypercholesterolemia but decreased to the control level after 6 weeks of hypercholesterolemia. In rabbits with 8 months of hypercholesterolemia the frequency and area of defects outside plaques did not differ from the control group. In the group with hypercholesterolemia for 8 months 39.2% of the plaque surface contained endothelial cells in which there were no distinct silver-stained cell borders. Kevex X-ray spectrometric data of silver topography indicated that the plaque surface without distinct cell borders was not an area devoid of cells. The data obtained do not support the assumption that morphological endothelial injury is the structural precursor of plaque formation.
Atherosclerosis 1982 Feb
PMID:Quantitative SEM analysis of injury to the endothelium of rabbit aorta and carotid artery during experimental atherosclerosis. 706 67

Ultrastructural autoradiography has been used to test the hypothesis that atherosclerotic regions of vessels differ with respect to lipoprotein uptake and localization. White Carneau pigeons, in which the prevalence and localization of aortic lesions are highly predictable, were fed a 0.25% cholesterol-supplemented diet to accelerate atherosclerosis. One hour prior to necropsy the birds were given a single intravenous injection of homologous [125I]LDL (low-density lipoprotein). Plasma die-away and tissue distribution of label were determined, and after the birds had been killed, the aortas, spleen and liver were processed for electron microscope autoradiography. Initial [125I]LDL uptake was rapid, with 35% of the label removed within 30 min. Predominant accumulation was in the liver, followed by the lung, kidney, the spleen and the aorta, in which the [125I]LDL level was approximately 4% that of the liver. Autoradiographic analysis documented hepatocyte (33%) and Kupffer cell (19.9%) localization in the liver and reticuloendothelial cell (57.4%) localization in the spleen. The aortic analysis involved serially sectioned lesions for direct comparison of non-lesion, lesion/non-lesion interface (edge) and deep lesion regions. Analysis of 2275 silver grains documented a ten-fold increase in LDL accumulation at the lesion edge (as compared to adjacent non-lesion) where macrophage foam cells contained more than 70% of the label. The other 30% was distributed equally among endothelium, the intimal matrix and smooth muscle cells. This distribution changed with more complex (deeper) lesions, although grain density in the complex lesions was comparable to the edge. In the complex regions, macrophage foam cell grains were reduced to 37%, whereas smooth muscle cell (22%) and the extracellular matrix (24%) label were both increased. These studies substantiate enhanced accumulation of lipoprotein specifically at lesion sites in the aorta and demonstrate a shift from macrophage localization at the developing edge to smooth muscle cell and the extracellular matrix in more complex deeper lesions.
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PMID:Localization of lipoprotein in pre- and post-transition atherosclerotic lesions following short-term incubation with [125I]LDL. 786 53

We have investigated the morphology of the aortic wall of newborn New Zealand White (NZW) (n = 10) and newborn Watanabe heritable hyperlipidemic (WHHL) (n = 10) rabbits. In both strains, lipid levels (cholesterol and triglycerides) were elevated above the concentrations expected. This was particularly evident in WHHL. The morphology of the aortas of NZW rabbits suggested an intensive biosynthetic and bioenergetic activity of endothelium. This was most evident in areas where blood flow underwent division. No major abnormalities were noted in the endothelium or subendothelium. In newborn WHHL rabbits, leucocyte adhesion (usually monocytes) to endothelium and migration into the subendothelium was apparent, particularly on the aortic arch and around areas of dividing blood flow in the thoracic aorta. Tuberous raised structures were present in low numbers and distributed randomly on the aortic wall. Endothelial cells had elevated nuclear zones projecting into the vessel lumen. At regions of blood flow division, endothelium was polygonal in shape and silver staining of cell borders was more intense. Fatty streaks were present at blood flow divisions and micro-plaque was seen. Transmission electron microscopy of fatty streak-like areas showed the presence of up to two layers of smooth muscle cells and in some areas, lipid-laden macrophages were seen. The presence of atherosclerotic lesions in newborn WHHL rabbits suggests that the process may commence in utero.
Atherosclerosis 1993 Jun
PMID:Evidence for the presence of early vascular lesions in newborn Watanabe heritable hyperlipidemic (WHHL) rabbits. 821 99

The oxidative modification of low density lipoprotein (LDL) has been implicated as an early step in the formation of atheromatous lesions. In vitro studies suggest it to be accelerated, or even initiated, by transition metals such as iron or copper in combination with a reducing agent. Even if such metals have been demonstrated in atheroma gruels, their origin and precise localisation within human atheroma are presently unknown. In the initial part of this study we applied Pearl's method, energy dispersive X-ray microanalysis, and a modified Timm sulphide silver method (SSM) to demonstrate the occurrence of iron in early atherosclerotic lesions from a number of consecutive autopsy cases with evident, general atheromatosis. With the very sensitive SSM, but not with the other techniques, we found foam cells to contain heavy metals with a mainly lysosomal localization. On the basis of the hypothesis that such a lysosomal accumulation of iron might be due to erythrophagocytosis by migrating tissue-bound macrophages that later develop into foam cells, we designed an in vitro model system where human monocyte-derived macrophages were exposed to artificially aged, UV-exposed erythrocytes. The macrophages were then exposed to LDL in serum-and iron-free RPMI medium, occasionally in the presence of the potent iron-chelator desferrioxamine. The capacity of macrophages to oxidise LDL was much enhanced following erythrophagocytosis, and the process was shown to involve secretion of iron. Consequently, LDL oxidation was greatly inhibited by desferrioxamine. We conclude that iron may be exocytosed by macrophages that previously had their lysosomal apparatus enriched with iron, e.g. due to erythrophagocytosis. Oxidation of LDL may result in ensuing foam cell-formation secondary to scavenger-receptor mediated endocytosis by macrophages.
Atherosclerosis 1996 Jul
PMID:Iron in human atheroma and LDL oxidation by macrophages following erythrophagocytosis. 880 Apr 94

Morphofunctional reorganization was studied of endothelium during the stage of formation of alimentary atherosclerosis and in experimental hyperadrenalinemia using transmission electronic microscopy and histochemistry together with silver nitrate impregnation of aortal endothelial monolayer. Certain morphofunctional equivalents have been established for the vascular wall exposure to the above factors, indicative of their unequalability and possibility of potentiation under combination. In both cases, an interrelationship similar in character has been shown between intensity of the endothelial reciprocal response and its regional morphofunctional features.
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PMID:[The characteristics of the morphofunctional restructuring of the aortic endothelium in food-related atherosclerosis and hyperadrenalinemia]. 1020 51

About 50 mg of silver leaf (metallic silver) was given daily by mouth to 30 healthy volunteers for 20 days. A statistically significant hypophospholipidemic, hypotriglyceridemic, hypocholesterolemic and hypoglycemic effect was observed. This was accompanied by a less marked fall in total lipids and significant rise in HDL-cholesterol. In addition, a decrease in plasma enzymes - alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), creatine phosphokinase (CPK), gamma glutamyl transpeptidase (GGT) and lactate dehydrogenase (LDH) was noted. This was statistically significant for all enzymes except CPK. The safety of ingested silver foil is indicated by absence of pathology in urine and unaltered levels of protein and albumin in the plasma. These observations suggest that silver could be beneficial in conditions like diabetes mellitus, obesity and atherosclerosis.
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PMID:Effect of silver leaf on circulating lipids and cardiac and hepatic enzymes. 1023 75

Apolipoprotein E (ApoE) plays an important role in cholesterol and triglyceride metabolism, being one of the major structural components of chylomicrons and very low density lipoprotein (VLDL) remnants. ApoE functions as a ligand in the receptor-mediated uptake of these remnants from the blood by the liver. A variant form of ApoE, apolipoprotein E*3-Leiden, shows reduced affinity for the low density lipoprotein (LDL) receptor, and results in the dominant expression of type III hyperlipoproteinemia. Two-dimensional electrophoresis (2-DE) has been used to characterise protein expression in serum samples from control and transgenic mice expressing the human ApoE*3-Leiden mutation, fed a cholesterol-rich diet, and transgenic mice fed a normal diet. For the identification of proteins, single silver-stained spots were excised from the 2-DE gels and subjected to in-gel enzymatic digestion. Extracted peptides were analysed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS). This proteomic approach has enabled the ApoE*3-Leiden variant to be positioned in a 2-DE separation of serum proteins, and has identified changes in the expression of haptoglobin, indicating that this protein may provide a marker for the potential onset of atherosclerosis.
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PMID:Phenotyping apolipoprotein E*3-leiden transgenic mice by two-dimensional polyacrylamide gel electrophoresis and mass spectrometric identification. 1093 69

Potential pharmacological applications in the areas of oncology, dermatology, diabetes, and atherosclerosis of synthetic analogs of retinoic acid that target a specific nuclear receptor and/or biological response have generated great interest in the development of new retinoid and rexinoid drugs. The pan-retinoic acid receptor antagonist AGN 193109 has been previously reported to elevate CYP1A1 levels, implicating the aryl hydrocarbon receptor (AhR) as an additional target for this retinoid. AhR is a cytosolic ligand-dependent transcription factor that, in conjunction with the AhR nuclear translocator (Arnt), binds to dioxin response elements (DREs) located in the promoter region of target genes, such as CYP1A1, and induces their transcription. The purpose of these studies was to determine whether additional synthetic retinoids were capable of elevating CYP1A1 levels and to examine the mechanism of this increase in CYP1A. Two additional retinoids, AGN 190730 and AGN 192837, were found to be potent inducers of DRE-driven transcriptional activity; AGN 190730 was the most potent. Moreover, electrophoretic mobility-shift assays demonstrate that AGN 190730 can transform AhR into its active DNA recognition form. In addition, trypsin digestion of AGN 190730-treated AhR reveals a conformational change in the protein similar to the conformational change of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-bound AhR. Finally, competitive binding studies demonstrate that AGN 190730 can inhibit the binding of TCDD to AhR. The sum of the data demonstrates that some synthetic retinoids in addition to activating the retinoic acid receptor/retinoid X receptor pathway are capable of binding to AhR and activating the AhR/Arnt pathway.
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PMID:Unique property of some synthetic retinoids: activation of the aryl hydrocarbon receptor pathway. 1180 58


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