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)

Neutral, uncharged binding sites for calcium ions are proposed for elastin and collagen. The sites utilize, particularly from a conformational viewpoint, the most striking feature of the amino acid composition, that is, the high glycine content. Glycines favor the formation of beta-turns and associated conformations that are known, from studies on ion-transporting antibiotics, to interact with cations. By analogy with certain antibiotics, which are uncharged polypeptides and depsipeptides that bind cations by coordination with neutral acyl oxygens, it is proposed that calcium-ion binding also utilizes uncharged coordinating groups, i.e., neutral sites, in the protein matrix. The protein matrix, which becomes positively charged by virtue of the bound calcium ions, attracts neutralizing phosphate and carbonate ions, which then allow further calcium ion binding. The driving force is, therefore, the affinity of calcium ions for the neutral nucleation sites. The charge neutralization theory of calcification suggests a fundamental role of organic anions, for example sulfated mucopolysaccharides, in regulating bone formation and in retardation of atherosclerosis. The proposed mechanism contains elements that tend to unify several theories on the pathogenesis of atherosclerosis.
 ...
PMID:Neutral sites for calcium ion binding to elastin and collagen: a charge neutralization theory for calcification and its relationship to atherosclerosis. 425 54

Several investigators have observed increased levels of esterified oleic acid in tissue cholesterol esters and phospholipids of atherosclerotic humans and cholesterol-fed animals. However, the cause of this is still unknown. Increased synthesis, increased esterification, or both of oleic acid can account for this. In the present investigation, hepatic synthesis of oleic acid is studied in cholesterol-fed rabbits. A nearly 3-fold increase in oleic acid synthesis was observed after 3 weeks of cholesterol feeding. This increase continued for at least 6 weeks. Since acyl acceptors like glycerol-3-phosphate are known to increase liver oleic acid synthesis it is possible that the observed increased in oleic acid formation was partially due to an increased availability of acyl acceptors in the system.
Atherosclerosis 1982 Jan
PMID:Increased liver oleic acid synthesis in cholesterol-fed rabbits. 612 54

New observations portray calcification processes as similar whether occurring normally or pathologically. Most forms of calcification are initiated by membranous organelles, ie, extracellular, calcifying "matrix vesicles" or intracellular mitochondria. Matrix vesicles promote calcification through calcium-binding phospholipids and phosphatase activity. Mitochondria use a forceful, inwardly directed Ca and phosphate transport mechanism. After mineral initiation, the proliferation of mineral crystals is dependent on regulatory factors, such as extracellular Ca2+ and PO4(3-) and other mineral inhibitors and promoters. Calcific diseases are defined as those in which (1) Ca uptake is early, (2) calcification is importantly related to dysfunction, and (3) the control of calcification may lead to decreased morbidity or enhanced diagnostic capability. Calcific diseases include such well-known entities as crystal deposition arthritis, atherosclerosis, calcific valvular sclerosis, tumor calcification, dental plaque, and dysfunctional calcification occurring in implanted cardiovascular devices.
 ...
PMID:Calcific diseases. A concept. 630 5

Matrix vesicles are widely regarded as the initial site of calcification in epiphyseal growth plate cartilage, in growing bone and in predentin. This opinion has recently been challenged on grounds that the early aqueous methods used for electron microscopic tissue preparation may have produced an erroneous picture by causing mineral dislocation. However, this argument has now been refuted by multiple investigators throughout the world using a variety of anhydrous methods coupled with electron probe analysis to show convincingly that matrix vesicles are, indeed, associated with initial mineral. Matrix vesicles appear to mineralize by concentrating calcium and phosphate at a protected site close to the inner leaflet of the vesicle membrane. Calcium may be attracted by its affinity for acidic phospholipids of the vesicle membrane, and phosphate may be concentrated by the action of transmembrane phosphatases of the matrix vesicle membrane. Evidence is accumulating to suggest that alkaline phosphatase of the matrix vesicle membrane functions as a phosphotransferase or phosphate vector, transporting PO4 across the vesicle membrane. The mechanism(s) of matrix vesicle biogenesis are discussed including budding from the plasma membrane (for which there is much support), cell degeneration (for which there is gathering support), extrusion of intracytoplasmic vesicles (for which there is weak support), and extracellular subunit self-assembly (for which there is little support). It is suggested that none of these mechanisms is necessarily exclusive, thus more than one mechanism may function in the same tissue. Finally, it is noted that in many calcific diseases, ranging from arthritis to atherosclerosis, mineralization is initiated by extracellular membrane-invested vesicles which are probably analogous to the matrix vesicles of skeletal tissues.
 ...
PMID:Mineralization by matrix vesicles. 638 26

In specimens from the superficial temporal artery (STA) and middle cerebral artery (MCA), obtained during STA-MCA anastomosis, green fluorescent varicose fibers of sympathetic nerves were clearly visible with both formaldehyde-glutaraldehyde and sucrose-potassium phosphate-glyoxylic acid wet-histofluorescent techniques. These fibers were fairly thick, were densely packed and had a meshwork-like arrangement. Fluorescent terminals were seen both in the adventitia and in the outer muscular layer of the media in both STA and MCA specimens. They were more often observed in patients with prominent atherosclerosis in these vessels. The present study suggests the possible role of sympathetic nerve terminals in the development of vasospasm and occlusive lesions in cerebral vessels. It may also help to explain the marked constriction and transient occlusion following a STA-MCA bypass procedure.
 ...
PMID:Sympathetic nerve terminals in the tunica media of human superficial temporal and middle cerebral arteries: wet histofluorescence. 640 79

This preliminary study describes effects of two pharmacologic agents on erythrocyte behavior. Increased erythrocyte aggregation has been proposed as important in the pathogenesis of a number of disorders, but the exact mechanism by which it plays a role in disease production remains unclear. Several anionic amphophiles have been reported to benefit diabetic vascular disease and atherosclerosis. If anionic amphophiles enter the erythrocyte plasma membrane they can increase its negative charge, reducing the energy of attraction between red blood cells and diminishing erythrocyte aggregation. Erythrocytes were studied after suspension in phosphate-buffered saline containing dextran as an aggregation-promoting agent. A marginal reduction of the suspension's viscosity was found at low shear rate when 2,5- dihydroxybenzene sulfonate was added. Additionally, erythrocyte sedimentation rate was marginally influenced. Both dihydroxybenzene sulfonate and acetylsalicylate protected human erythrocytes from hemolysis at concentrations from 10(-3) to 10(-5) M. The removal of erythrocyte sialic acid using neuraminidase to reduce surface negative charge led to unequivocal interference with aggregation (MAI technique of CHIEN et al., J. Gen. Physiol., 1973) by both anionic amphophiles were studied. Dihydroxybenzene sulfonate and actylsalicylate reduced the aggregation propensity of sialic-free erythrocytes, suggesting that the effect on the low shear rate viscosity of sialic acid-containing erythrocytes, though modest, is real.
 ...
PMID:Effect of anionic amphophiles on erythrocyte properties. 658 20

The results of morphological studies on the structure of mineral deposits in the walls of major arteries in atherosclerosis are presented. Calcium deposits looking like petrificates and microgranular deposits were found. The petrificates consisted of microgranular, microcrystalline and macrocrystalline deposits of calcium salts. In the arterial wall, the crystals consisted of calcium phosphate and calcium carbonate. The relationship between the destruction of elastic fibers and elastic membranes and calcification of the vascular wall was confirmed.
 ...
PMID:[Structure of the mineral deposits in major arterial walls in calcinosis (based on scanning electron microscopic data)]. 663 99

The incidence of cardiovascular disease is lower in women than in men, but is raised in men with prostatic cancer treated with estrogens. Changes of the plasma lipoproteins are related to the development of ischaemic cardiovascular disease and can be brought about by hormonal treatment. We have therefore studied plasma lipoproteins during estrogen treatment and after orchidectomy. 16 patients with prostatic carcinoma were treated with ethinyl estradiol daily by mouth and polyestradiol phosphate intramuscularly once a month. 15 other patients were treated by bilateral orchidectomy. Cholesterol (C), triglyceride (TG), and phospholipid (PL) concentrations in plasma and in the very low density (VLDL), low density (LDL) and high density lipoprotein (HDL) fractions were determined before starting treatment and 2 weeks and 8 weeks later. In the estrogen treated group the mean plasma C concentration decreased by 14 and 10%, while the mean HLD-C increased by 23 and 53%, and the mean LDL-C decreased by 24 and 25% at 2 and 8 weeks respectively. The mean PL concentration in HDL increased by 36 and 79% while that in LDL decreased by 12 and 18%. The mean plasma TG concentration was increased by 36 and 46%, mainly reflecting a rise of TG in the HDL-LDL fraction. Orchidectomy created only slight changes of plasma lipids. After 8 weeks the mean C concentration in plasma was raised by 10% and the mean PL concentration by 11%, owing to a 13% rise in the mean HDL-PL level. The changes in plasma lipoprotein pattern created by high doses of estrogens are mainly thought to protect against the development of atherosclerosis. The slight changes that take place after orchidectomy can hardly affect the incidence of cardiovascular disease.
 ...
PMID:Plasma lipoproteins during anti-androgen treatment by estrogens or orchidectomy in men with prostatic carcinoma. 726 28

Atherosclerosis occurs at an accelerated rate in patients with diabetes mellitus. Since some proteins undergo nonenzymatic glycosylation in diabetic patients and because certain chemical modifications of low density lipoproteins produced alterations in their interactions with certain cultured cells, a fact that may be relevant to atherogenesis, we investigated the effect of in vitro glycosylation on cell-related properties of low density lipoproteins. Glycosylation was carried out by incubating LDL (1-10 mg LDL-protein/ml) with glucose (0-100 mM) in 0.5 M phosphate buffer, pH 8.0, at 37 degrees C. The amount of glucose incorporated into LDL after 1-2 wk of incubation was estimated to be in the range of 1-10 mol/mol LDL-protein. Amino acid analysis of glycosylated LDL showed that glucose was covalently bound to lysine residues. In studies with cultured human fibroblasts, glycosylated LDL was internalized and degraded significantly less than control LDL, in proportion to the estimated degree of glycosylation (12% of control for the most extensively glycosylated LDL). Glycosylation of LDL also impaired significantly its ability to stimulate cholesteryl ester synthesis by cultured fibroblasts. Glycosylated LDL did not stimulate cholesteryl ester synthesis in rat peritoneal macrophages. If glycosylation of LDL occurs in diabetic patients, some pathophysiologic consequences related to the increased incidence of atherosclerosis in these patients may result.
 ...
PMID:Nonenzymatic glycosylation of low density lipoproteins in vitro. Effects on cell-interactive properties. 727 89

Calcified atherosclerotic aorta was examined for proteolipid capable of nucleating apatite, the crystal species of aortic calcification. Appropriate tissue pieces were decalcified with dilute formic acid and extracted with chloroform-methanol. Lipid fractionation yielded proteolipid which, upon incubation in metastable calcium phosphate solution, induced apatite crystallization. The proteolipid was partially characterized as a hydrophobic protein, acidic phospholipid complex. It resembles the nucleator previously demonstrated for bone matrix calcification.
Atherosclerosis 1980 Feb
PMID:Calcification by proteolipid from atherosclerotic aorta. 735 56


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