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)

We examined immunohistochemically 104 formaldehyde-fixed, paraffin-embedded, human autopsy aortic specimens for C-reactive protein (CRP) presence and localization. In addition, we correlated immunoreactivity with a spectrum of the following histologic categories: normal aorta, fatty streak, atheromatous plaque, and fibrous plaque. Using appropriate controls, we confirmed CRP immunoreactivity in 3.3% of normal specimens, 75% of fatty streaks, 90.2% of atheromatous plaques, and 64.6% of fibrous plaques. Immunoreactivity in fatty streaks was located around collections of foam cells. Immunoreactivity in atheromatous plaques was in a bandlike distribution corresponding to the pale-staining insudative zone frequently seen in such lesions. The correlation and localization of CRP immunoreactivity in atherosclerotic lesions presented here suggests a functional role for CRP in the pathogenesis of atherosclerosis. Our results encourage efforts to determine more precisely the physiologic contributions of CRP to the development and exacerbation of atherosclerosis.
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PMID:C-reactive protein immunohistochemical localization in normal and atherosclerotic human aortas. 243 57

We have studied the ability of particulate stimuli to induce the release of reactive oxygen metabolites from sub-cultured monolayers of human endothelial cells. Basal release of superoxide (O2-) and hydrogen peroxide from undisturbed monolayers was very low (108 pmol O2- and 75 pmol H2O2 in 3 h from dishes of 3 X 10(5) cells). Addition of 1-micron diameter polystyrene microspheres, which were phagocytosed by the cells progressively, caused a dramatic increase in release of both metabolites; by 3 h, a 13.5- and 6.6-fold increase over controls was observed respectively (P less than 0.001). Addition of formaldehyde-fixed human platelets or chylomicron-size lipid particles also increased production of reactive oxygen species. Similar rises in H2O2 and O2- production were induced by treatment with 10(-7) M phorbol myristate acetate. Pretreatment of endothelial cells with neuraminidase, heparinase or heparitinase to alter their glycocalyx composition substantially enhanced the effect of microspheres on H2O2 and O2- generation. We conclude that the interactions of particles, including platelets and lipids, with endothelial cells leads to the generation of significant pericellular levels of reactive oxygen species. These metabolites can oxidise a wide variety of nearby molecules, leading to cell damage and altered uptake characteristics for lipoproteins containing peroxidized lipids. These effects are exacerbated when endothelial cell glycocalyx composition is disrupted.
Atherosclerosis 1988 Jul
PMID:Generation of reactive oxygen metabolites by phagocytosing endothelial cells. 285 Aug 6

It has been shown that monocytes are present in early atherosclerotic lesions and in mechanically-injured arterial intima, but direct morphological tracing of specific leukocyte populations into such areas has been lacking. A method for FITC-labelling of leukocytes was therefore evaluated for monocyte studies. Monocyte (95% pure) populations were isolated from blood by counterflow centrifugation and labelled by incubation with free fluorescein isothiocyanate 1-hydrochloride (FITC) in Hank's balanced salt solution. FITC-labelled monocytes showed glass adherence, spreading and migration, as well as acid phosphatase positivity and phagocytosis for up to 20 days in tissue culture. For in vivo experiments, hypercholesterolemic (H) and normal (N) swine were bled repeatedly, and monocyte populations were isolated, labelled and reinjected. Labelled cells were found in blood samples. Animals were killed after 9 days, and formaldehyde-fixed and frozen samples of aortae were studied en face and/or sectioned and examined microscopically under fluorescence. FITC-labelled leukocytes could be found adherent to sites of thickened intima but not to normal areas. Labelled cells were also detected within atherosclerotic lesions. These results show the feasibility of the labelling technique and provide direct visualization of monocyte recruitment from the blood into atherosclerotic and lesion-prone areas.
Atherosclerosis 1988 May
PMID:Visualization of monocyte recruitment into atherosclerotic arteries using fluorescent labelling. 313 79

Shear stress activated platelets undergo aggregation in the presence of large or unusually large von Willebrand factor (vWF) multimers without the addition of ristocetin or any other exogenous chemical. This phenomenon may be analogous to the platelet aggregation that leads to thrombosis in the narrowed arteries and arterioles of patients with atherosclerosis or vasospasm. A triphenyl-methyl compound, aurin tricarboxylic acid (ATA), inhibits shear-induced, vWF-mediated platelet aggregation in platelet-rich plasma (PRP) in concentrations above 200 mumol/L and in buffer suspensions of washed platelets at a concentration of 0.1 mumol/L. In a concentration-dependent manner, ATA also inhibits ristocetin-induced, vWF-mediated platelet clumping in both fresh and formaldehyde-fixed platelet suspensions. This inhibition can be overcome by increasing the concentration of vWF, following the kinetics of first order competitive inhibition. ATA prevents the attachment to platelets of the largest vWF multimeric forms found in normal plasma and of the unusually large vWF multimers derived from endothelial cells. The rate of aggregation and degree of inhibition by ATA is not accounted for by the binding of ristocetin or calcium. Arachidonic acid- and adenosine diphosphate (ADP)-induced aggregation are not inhibited by ATA. Platelets incubated with ATA can be easily separated from the compound. However, ATA binds to large vWF multimeric forms and inhibits their ristocetin-induced interaction with platelet glycoprotein Ib. Because ATA also inhibits shear-induced, vWF-mediated platelet aggregation in vitro in the absence of ristocetin, it may be a useful prototype compound to impede the development of arterial thrombosis in vivo.
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PMID:Aurin tricarboxylic acid: a novel inhibitor of the association of von Willebrand factor and platelets. 326 93

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.
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PMID:Sympathetic nerve terminals in the tunica media of human superficial temporal and middle cerebral arteries: wet histofluorescence. 640 79

Cigarette smoking is a risk factor for atherosclerosis. It is conceivable that reactive chemical components in cigarette smoke may adversely affect reverse cholesterol transport at the level of lecithin: cholesterol acyltransferase (LCAT) and promote atherogenesis. Hence, the effect of cigarette smoke extract (CSE) on the activity of LCAT in human plasma was studied. When incubated with plasma, CSE caused both concentration- and time-dependent losses of LCAT activity. Addition of glutathione, but not ascorbate, to plasma prevented loss of LCAT activity caused by CSE. Incubation of plasma with some reactive aldehydes known to be present in cigarette smoke also inhibited LCAT activity. Among five aldehydes tested, acrolein was the strongest inhibitor of LCAT, with complete enzyme inhibition occurring at 1 mM. Acetaldehyde was the weakest inhibitor of LCAT, with 85% enzyme inhibition at 50 mM. Hexanal, formaldehyde, and malondialdehyde completely inhibited LCAT activity at 10, 50, and 50 mM, respectively. When plasma was incubated with 1 mM acrolein in the presence of 2.5 mM glutathione or dihydrolipoic acid, 100 and 57% of LCAT activity, respectively, remained after incubation. This finding suggest that reactive aldehydes may form adducts with certain free sulfhydryl groups functioning in the active site of LCAT to inhibit enzyme activity. It is concluded that reactive aldehydes are at least partially responsible for the reduction in LCAT activity in plasma treated with CSE.
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PMID:Inhibition of lecithin: cholesterol acyltransferase activity in human blood plasma by cigarette smoke extract and reactive aldehydes. 747 2

Previous angiographic observations have characterized transplant atherosclerosis as a generally diffuse and more distally severe disease with obliteration of secondary branches. However, it has not been firmly established that the disease is structurally and biologically more severe distally. We evaluated this hypothesis with computer-based digitization of subserial segments of the entire perfusion-fixed left anterior descending coronary artery (100 mm Hg for 1 hour with 10% formaldehyde solution) in 25 allografts at autopsy or explant (19 male and 6 female patients; mean age = 50 years, range 16 to 66; mean implant duration = 490 days, range 3 to 1610). The area, thickness, circumference of the intima and media, and the relative and absolute luminal narrowing were evaluated in a mean of 10 left anterior descending coronary artery sections per allograft. The percentage of luminal narrowing (intimal area/[intimal area + luminal area] x 100) was similar between proximal and distal segments of the left anterior descending coronary artery (45% versus 41%, p > 0.05), and the mean absolute intimal thicknesses (in millimeters) of proximal and distal segments of the left anterior descending coronary artery also were not different (0.32 versus 0.22, p > 0.05). In addition, the 95% confidence intervals for intimal thicknesses of proximal and distal segments were comparable. Because the absolute arterial size of proximal segments is naturally larger than that of distal segments (external diameter 9.37 versus 6.79, p < 0.0001), an appearance of progressive tapering may be visualized angiographically, even though the biologic severity of the disease is geographically uniform. Similarly, observations of obliterated secondary branches in distal segments may result from naturally smaller distal luminal areas which may be occluded by less intimal thickening than would be required proximally. These data emphasize that transplant atherosclerosis is biologically uniform from proximal to distal locations. Etiologic and pathogenetic studies on proximal or distal segments should be equally informative.
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PMID:Comparable proximal and distal severity of intimal thickening and size of epicardial coronary arteries in transplant arteriopathy of human cardiac allografts. 780 23

Scavenger receptors interact with a variety of modified proteins, mediate their endocytosis and degradation, and may play an important role in protein catabolism and pathogenic processes such as atherosclerosis, aging, and diabetes. Many scavenger receptors have been detected kinetically but few such binding proteins have actually been identified. Recently, we found that two membrane-associated proteins, gp30 and gp18, interact more avidly with albumins conformationally modified by chemical means or by surface adsorption to colloidal gold particles than with native albumin. In this study, we show that gp30 and gp18 behave similarly to other known scavenger receptors. Competition studies indicate a similar ligand binding profile to other known scavenger receptors. Polyanionic molecules (dextran sulfate, fucoidan, polyglutamic acid, polyinosinic acid, heparin) and modified albumins such as formaldehyde-treated or maleylated albumin (Mal-bovine serum albumin) competed with albumin conjugated to colloidal gold particles (A-Au) for the blotting of gp30 and gp18. A-Au and Mal-bovine serum albumin bound cultured endothelial cells with high affinity. Modified and native albumins were each internalized, but only modified albumins were then released degraded. Inhibition studies revealed that only the same molecules that were effective in blocking A-Au blotting of gp30 and gp18, also inhibited A-Au degradation. Addition of the lysosomotropic agent chloroquine resulted in more than 70% inhibition of degradation. Differential processing of A-Au by cultured smooth muscle and endothelial cells along with fibroblasts was observed in a manner consistent with gp30 and gp18 expression. Cumulatively, these results suggest that gp30 and gp18 may mediate the high affinity binding, endocytosis, and degradation of conformationally modified albumins but not native albumin.
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PMID:High affinity binding, endocytosis, and degradation of conformationally modified albumins. Potential role of gp30 and gp18 as novel scavenger receptors. 846 86

Methylamine can be converted by semicarbazide-sensitive amine oxidase (SSAO) to formaldehyde and hydrogen peroxide, which have been proven to be toxic towards cultured endothelial cells. We investigated whether or not these deaminated products from methylamine can exert potentially hazardous toxic effects in vivo. Long lasting residual radioactivity in different tissues was detected following administration of [14C]-methylamine in the mouse. Approximately 10% of the total administered radioactivity could even be detected 5 days after injection of [14C]-methylamine. Eighty percent of the formation of irreversible adducts can be blocked by a highly selective SSAO inhibitor, (E)-2-(4-fluorophenethyl)-3-fluoroallylamine hydrochloride (MDL-72974A). The residual radioactivity was primarily associated with the insoluble tissue components and the soluble macromolecules. Radioactively labelled macromolecules were fragmented following enzymatic proteolysis. Results suggest that the formaldehyde derived from methylamine interacts with proteins in vivo. In the streptozotocin-induced diabetic mice, both SSAO activity and the formation of residual radioactivity were found to be significantly increased in the kidney. Chronic administration of methylamine enhances blood prorenin level, which strongly suggests that uncontrolled deamination of methylamine may be a risk factor for initiation of endothelial injury, and subsequent genesis of atherosclerosis.
Atherosclerosis 1996 Feb
PMID:Formaldehyde produced endogenously via deamination of methylamine. A potential risk factor for initiation of endothelial injury. 864 60

To investigate the effects of hyperinsulinemia on the myocardial vessels, long acting insulin (mixtard, a combination of 30% regular human insulin and 70% NPH human insulin) was injected daily for 8 weeks, intraperitoneally, in two strains of rats, normotensive WKY and hypertensive SHR. There were four groups in all, a control group, and an insulin-injected group in each strain. The drinking water contained 10% glucose to prevent hypoglycemia in the insulin-injected rats. At the end of the 8 weeks experimental period, after measuring blood pressure and taking blood for the determination of glucose, urea, creatinine, and insulin, the rats were killed. The organs were fixed in formaldehyde. The blood glucose levels were higher at the end of the experiment, in both the placebo- (saline)-injected and the insulin-injected rats. Blood pressure rose significantly only in the insulin-injected SHR. The intramyocardial arterioles in the insulin-injected SHR had a significantly thicker vascular wall than the placebo-injected SHR, as represented by the vessel wall to lumen ratio, because of hypertrophy of the media. When compared with the placebo injected WKY rats, there was a higher wall/lumen ratio of the intramyocardial arterioles in the insulin-injected WKY, but the difference did not reach significance. Heart weights factored by body weights was significantly higher in insulin-injected as compared with placebo-injected SHR. Myocardial infarctions were observed in four of eight rats in the insulin-injected SHR group despite the fact that there were no signs of atherosclerosis or intimal thickening. It is possible that the increase in heart weight and the probable increase in metabolic activity resulting from hyperinsulinemia, together with the increased oxygen demand of the myocardium and the arteriolar narrowing, may have contributed to the occurence of myocardial infarctions in the absence of atherosclerotic coronary occlusion.
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PMID:Hyperinsulinemia induces myocardial infarctions and arteriolar medial hypertrophy in spontaneously hypertensive rats. 919 11


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