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)

The rheology of red blood cells in patients with atherosclerosis is abnormal. To investigate this further, the authors examined the effect of sera from patients with atherosclerosis on the handling of calcium by the erythrocyte membrane. Normal erythrocytes were filled with a photoprotein (aequorin) which emits light on contact with calcium. These photoprotein-loaded normal erythrocytes were then incubated overnight with the serum from normal subjects (n = 34) and from patients with atherosclerosis (n = 30). There was a significant decrease in basal calcium leakage, as measured by the amount of light produced following the addition of triton X-100. Induced calcium influx, as measured by the amount of light produced following the addition of ionophore A23817, was significantly greater in the photoprotein-loaded erythrocytes incubated overnight with the serum from patients with atherosclerosis compared with those incubated with the serum from normal subjects (p < 0.01). This modulation of Ca2+ handling in erythrocytes by a serum factor from patients with atherosclerosis could account for the alterations in erythrocyte function, such as red cell deformability, observed in atherosclerosis.
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PMID:Abnormal effect of sera from patients with atherosclerosis on calcium influx into normal erythrocytes. 133 14

PAF-acether, a naturally occurring phospholipid, is a potent activator of various biological processes, including platelet aggregation. The mechanisms of action of PAF are largely unknown. We have found that the psychotropic triazolobenzodiazepine drugs, alprazolam and triazolam, potently (IC50 less than 1 microM) inhibit PAF-induced shape change, aggregation and secretion of human platelets. These effects are specific for PAF-activation, since the responses of human platelets to other agonists (ADP, thrombin, epinephrine, collagen, arachidonate and the Ca++ ionophore, A23187) are not inhibited by these triazolobenzodiazepines. The action of triazolobenzodiazepines on PAF-induced platelet function has clinical relevance, especially in diseases where enhanced platelet aggregability may lead to thrombosis and atherosclerosis. In addition, the ability of triazolobenzodiazepines to inhibit other PAF-mediated cellular-responses, such as anaphylactic shock or bronchoconstriction, suggests that these drugs may be useful in preventing several known pathophysiological effects of PAF. The specific antagonism of PAF action by psychotropic drugs also suggests that PAF or PAF-like phospholipids may play a role in neuronal function. This possibility was tested by examining the effects of PAF on neural cells of the clonal line NG108-15, grown in culture in a chemically defined, serum-free medium. Low concentrations of PAF (0.5-2.5 microM) induced neurite extension in NG108-15 cells, whereas higher concentrations (greater than 3 microM) were cytotoxic. Using NG108-15 cells preloaded with aequorin, it was found that PAF causes an increase in intracellular ionized calcium concentration, which is dependent on the presence of extracellular calcium. These results suggest that PAF-induced Ca++ uptake may play a role in neuronal development, and that circulating PAF may contribute to the neuronal degeneration caused by the exposure of neural tissues to blood in situations such as spinal cord injury, trauma, or stroke.
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PMID:Interactions of the alkyl-ether-phospholipid, platelet activating factor (PAF) with platelets, neural cells, and the psychotropic drugs triazolobenzodiazepines. 289 25

Atherosclerosis is a progressive disease in which its clinical sequelae are manifest with increasing frequency as individual age. The present study seeks to better understand the mechanisms underlying this process by utilizing our previously-characterized rat model of early atherosclerosis induction to evaluate the effect of atherogenic plasma lipids on intracellular ionized calcium levels in rat platelets. Sprague-Dawley male rats were infused i.v. with 20% Lipofundin-S, a triglyceride-rich emulsion shown by us in previous studies to induce early athero-sclerosis and platelet hyperactivity. Twenty four hrs after the last infusion, blood was obtained by cardiac puncture. Washed platelets were loaded with aequorin, stimulated with ADP, and [Ca++]i was determined by measuring luminescence in platelets from lipid-infused vs. control rats. In platelets isolated from lipid-infused rats, [Ca++]i levels were 34% higher (p < or = 0.05) than in platelets from control animals. In addition, the mean, median, and mode diameters of platelets from lipid-treated rats were significantly greater (p < or = 0.001) than those of platelets from controls. With ADP as the aggregating agent, nifedipine at 1 microgram/ml caused a 27% (p < or = 0.05) inhibition of [Ca++]i release in platelets from lipid-treated rats, but showed no inhibitory action in platelets isolated from control animals. Hyperlipidemia results in elevated platelet [Ca++]i levels, with a concomitant increase in cell size, both indicating enhanced platelet function. Nifedipine modulates this increased activity in platelets isolated from lipid-infused rats, but not in cells from control animals.
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PMID:Intracellular ionized calcium ([Ca++]i) mobilization in platelets from rats receiving atherogenic lipids. Modulation by nifedipine. 886 50

In a recent clinical study, tranilast, an anti-allergic agent, was shown to reduce the rate of coronary restenosis after percutaneous transluminal coronary angioplasty, although the mechanism of this effect is unclear. The present study was undertaken to investigate the effects of tranilast on contraction and Ca2+ movement of the coronary arteries. We characterized the effects of tranilast on isometric force and aequorin-estimated intracellular Ca2+ concentrations ([Ca2+]i) of porcine coronary artery strips. Tranilast concentration-dependently (10-500 microM) inhibited histamine (3 x 10(-5) M)-induced contraction of the coronary arteries. A similar tendency was observed in the response to high K+ (30 mM) stimulation. Histamine caused phasic and tonic increases in [Ca2+]i, and high K+ caused a tonic increase in [Ca2+]i of smooth muscle, both of which were significantly suppressed in the presence of tranilast. These results suggest that tranilast inhibits the contraction of coronary arteries by inhibiting both Ca2+ influx from extracellular environment and Ca2+ release from intracellular Ca2+ stores, which might be related to its preventive effect on restenosis after coronary angioplasty.
Atherosclerosis 1997 Apr
PMID:Tranilast inhibits contraction and Ca2+ movement of porcine coronary arteries. 912 55

Chlamydia pneumoniae has been associated with chronic conditions such as atherosclerosis and coronary heart disease but the precise role of this intracellular bacteria in the pathogenesis of these diseases is not well defined. Several techniques have been developed for detection of C. pneumoniae in atheromatous lesions, however it remains unclear whether persistent forms of the organism and/or actively replicating bacteria contribute to associated pathology. The aim of this study was to utilize nucleic acid sequence based amplification (NASBA) technology together with a highly sensitive aequorin bioluminescent hybridization assay for the detection of C. pneumoniae ompA mRNA transcripts. A NASBA targeting the ompA gene of C. pneumoniae was developed, and the sensitivity was evaluated using both C. pneumoniae ompA RNA generated in vitro, and purified C. pneumoniae inclusion forming units (IFU). C. pneumoniae NASBA was capable of detecting between 100 and 1000 ompA RNA molecules and could detect 0.2 IFU of C. pneumoniae using the aequorin bioluminescent assay. The sensitivity of the bioluminescent assay was at least 10-fold higher than Northern blot detection. The linearity of NASBA amplification was assessed in time-course amplification experiments with different input numbers of RNA molecules. When NASBA products were analyzed during the linear phase of amplification, the dynamic range of bioluminescent detection extended over 8-log units of input RNA copy number. NASBA amplification coupled with bioluminescent detection may prove to be a useful molecular tool for the detection, quantitation and analysis of differentially expressed chlamydial genes during various stages of infection and disease pathology or for other mRNAs of interest in different disease processes.
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PMID:Nucleic acid sequence based amplification (NASBA) of Chlamydia pneumoniae major outer membrane protein (ompA) mRNA with bioluminescent detection. 1097 44