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)

A densitometric technique was established to investigate quantitative changes in endothelial permeability for horseradish peroxidase (HRP), mol. wt. 40,000 daltons, in rabbit carotid artery. Repeated weak electrical stimulations of rabbit carotid arterial walls with implanted electrodes lead to fibromuscular plaques mainly beneath the anode. It could be demonstrated that there exists a typical growth curve of the plaques dependent on the number of days of electrostimulation, with a fast proliferation rate of smooth muscle cells in the first 2 weeks of electrostimulation, and an increasing retardation of proliferation during the next 4 weeks. Endothelial permeability for HRP increases in close relation to the plaque development. Intravenous applications of single doses of the calcium entry blockers flunarizine or nimodipine are able to inhibit the increased permeability of the endothelial lining covering arteriosclerotic plaques. The intensity of the inhibitory action of these calcium antagonists correlates with the size of the arteriosclerotic plaques in inverse proportion, but nevertheless in large plaques an inhibitory effect is seen.
Atherosclerosis 1989 Feb
PMID:Densitometric measurement of increased endothelial permeability in arteriosclerotic plaques and inhibition of permeability under the influence of two calcium antagonists. 271 59

Myocardial ischaemia results from complex interrelated processes involving progression of atherosclerosis, thrombosis, coronary spasm, platelet aggregation and local release of products from the arachidonic acid cascade. Endothelium-dependent responsiveness contributes to the local regulation of coronary blood flow, and the presence of endothelial damage may result in enhanced contraction of the smooth muscle. Drugs which have been used for the treatment of angina pectoris are able to reduce myocardial oxygen consumption. This concept will further be developed in the near future with beta-blocking agents with vasodilating properties, potent long acting nitrates (nicorandil), bradycardic agents (AQA 39 or AS-AH 208), and new calcium antagonists. However, future prospects in the treatment of angina pectoris include: drugs modifying the arachidonic acid cascade by increasing synthesis or release of prostacyclin (nafazatrom) or decreasing prostacyclin degradation (almitrine), or blocking thromboxane A2 synthetase (dazoxiben) or thromboxane A2 receptors (BM 13177) or, blocking the lipoxygenase pathway (nafazatrom) or prostacyclin analogues (iloprost); more clot-specific thrombolytic agents and new oral anticoagulant drugs; free-radical scavengers such as superoxide dismutase, catalase or peroxidase and drugs inhibiting xanthine-oxidase; anti-platelet drugs such as ticlopidine which blocks the fibrinogen receptors of platelets; drugs preventing the progression of atherosclerosis lesions such as nifedipine or verapamil in animals fed high-lipid diets; drugs which could modify myocardial metabolism during ischaemia. In this context, trimetazidine acts through prevention of ischaemia-induced decrease in ATP cellular storages, inhibition of potassium leak, decrease in free-radical production and thromboxane A2 synthesis and increase in prostacyclin synthesis. These new concepts provide an important contribution to the understanding of the pathophysiology of myocardial ischaemia. This explains the considerable development of pharmacological research for new agents in the treatment of angina pectoris.
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PMID:[Treatment of angina pectoris. New perspectives]. 294 45

This study localized Factor VIII-related antigen (FVIIIRAg) directly in the intramural coronary arteries of patients with coronary artery disease (CAD). Assays were performed on myocardial autopsy sections from 17 patients with and 15 patients without CAD, using a monospecific FVIIIRAg antibody in the peroxidase-immunoperoxidase technic. FVIIIRAg was quantified by a FVIIIRAg index (FRI), as a numerical score based on distribution, thickness, and extension of immunostaining. The mean FRI for the CAD patients was 55 +/- 11 and that for the control patients 12 +/- 5 (P less than 0.001). The increased amounts of in situ FVIIIRAg suggest this glycoprotein may be involved in the pathogenesis of atherosclerosis.
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PMID:Coronary artery deposition of factor VIII-related antigen in ischemic heart disease. 309 35

In autoimmune hyper- or dislipidemia secondary to a monoclonal antilipoprotein gammapathy, immunoglobulin-lipoprotein (Ig-Lp) complexes are found in the circulating blood. In order to determine their possible significance in common types of hyperlipidemia we compared the Ig-Lp content of sera from 98 healthy blood donors and 155 outpatients from a Lipid Clinic, including 91 cases of hypercholesterolemia (55 familial and 36 non-familial), 15 cases of hypertriglyceridemia, 20 cases of mixed hyperlipidemia and 29 miscellaneous cases. Detection of the Ig-Lp was performed by an ELISA technique with polyclonal affinity purified anti-LDL + HDL as capture antibodies and peroxidase-labeled anti-Ig antibodies specific for IgA, IgG, IgM heavy chains as indicators. Two cases of monoclonal gammapathy (one IgA K and one IgG L) with dislipidemia served as positive controls for the test. IgG, IgA and IgM Lp were found in the sera of the blood donors, in very small quantities when compared with the monoclonal gammapathy cases. All three types of Ig-Lp were also found in the different hyperlipidemic populations studied. When blood donors were compared to hyperlipidemic patients, no difference was observed for IgG Lp. A significant increase in IgM Lp was found in patients with familial hypercholesterolemia (P less than 0.01). An increase in IgA Lp was also found in hypercholesterolemia, familial or not (P less than 0.01), and in patients with corneal arcus (P less than 0.0001), ischaemic disease (P less than 0.01), tendon xanthomas (P less than 0.05) or xanthelasma (P less than 0.05). Furthermore, in a group of 18 paired parents from 9 different families, positive interparent correlations were found for IgM Lp (r = 0.78; P = 0.013) and IgG Lp (r = 0.69; P = 0.038). Therefore IgM Lp may be markers for subpopulations of familial hypercholesterolemia, and IgA Lp markers for the risk of atherosclerotic ischemic disease and deposition of lipids in the cornea. It may be (1) that natural clones of autoanti-lipoprotein antibodies are responsible for the minute quantities of Ig-Lp found in normal people; (2) that the marked development of one of these clones is the cause of autoimmune hyper- or dyslipidemia and xanthomatosis associated with monoclonal gammapathy; (3) that the limited development of a clone produces the Ig-Lp particles found in hypercholesterolemic patients; (4) that there are types of Ig-Lp particles (IgA Lp) that may be harmful for tissues independently of hypercholesterolemia.
Atherosclerosis 1988 Dec
PMID:Immunoglobulin-bound lipoproteins (Ig-Lp) as markers of familial hypercholesterolemia, xanthomatosis and atherosclerosis. 324 Mar 31

We have examined whether the toxic effects of homocysteine on cultured endothelial cells could result from the formation and action of hydrogen peroxide. In initial experiments with a cell-free system, micromolar amounts of copper were found to catalyze an oxygen-dependent oxidation of homocysteine. The molar ratio of homocysteine oxidized to oxygen consumed was approximately 4.0, which suggests that oxygen was reduced to water. The addition of catalase, however, decreased oxygen consumption by nearly one-half, which suggests that H2O2 was formed during the reaction. Confirming this hypothesis, H2O2 formation was detected using the horseradish peroxidase-dependent oxidation of fluorescent scopoletin. Ceruloplasmin was also found to catalyze oxidation of homocysteine and generation of H2O2 in molar amounts equivalent to copper sulfate. Finally, homocysteine oxidation was catalyzed by normal human serum in a concentration-dependent manner. Using cultured human and bovine endothelial cells, we found that homocysteine plus copper could lyse the cells in a dose-dependent manner, an effect that was completely prevented by catalase. Homocystine plus copper was not toxic to the cells. Specific injury to endothelial cells was seen only after 4 h of incubation with homocysteine plus copper. Confirming the biochemical studies, ceruloplasmin was also found to be equivalent to Cu++ in its ability to cause injury to endothelial cells in the presence of homocysteine. Since elevated levels of homocysteine have been implicated in premature development of atherosclerosis, these findings may be relevant to the mechanism of some types of chronic vascular injury.
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PMID:Endothelial cell injury due to copper-catalyzed hydrogen peroxide generation from homocysteine. 351 79

The distribution of apolipoprotein E (apo E) immunoreactive substances (IRS) in atherosclerotic lesions and lesion-free areas of the aorta and coronary arteries obtained from 17 autopsied cases was studied using a specific anti-apo E serum and the unlabeled peroxidase-antiperoxidase (PAP) method. In fatty streak lesions of the aorta, many cells containing apo E-IRS were found in the deeper layer of the intima and diffuse staining of apo E in the extracellular spaces was also noted. In more advanced lesions apo E-positive cells could not be found. Immunohistochemical findings of coronary arteries differed distinctly from those of the aorta in that the apo-E-positive cells were absent in the deeper layer of the intima. The endothelial cells of coronary arteries, but not those of the aorta, showed positive staining for apo E.
Atherosclerosis 1986 Apr
PMID:Immunohistochemical localization of apolipoprotein E in atherosclerotic lesions of the aorta and coronary arteries. 351 33

In order to assess the possible utility of lectin binding to identify the cellular components of fixed arterial lesions we studied lectin binding in experimental rabbit and monkey vessels, as well as in human atherosclerotic arteries obtained at surgery. The avidin-biotin-peroxidase technique was used to localize the binding of the following biotinylated lectins: Concanavalin A (Con A), Dolicho biflorus agglutinin (DBA), soybean agglutinin (SBA), peanut agglutinin (PNA), Phaseolus vulgaris agglutinin (PHA), Ricinus communis agglutinin (RCA), wheat germ agglutinin (WGA), and Ulex europaeus agglutinin (UEA). PHA demonstrated specific cytoplasmic staining of macrophages in rabbit, monkey, and human tissues and differentiated macrophages from other cell types in atherosclerotic lesions. When morphometric comparisons were made between lesion PHA staining and another macrophage marker, acid lipase, very similar results were obtained. Con A, RCA, and WGA stained macrophages intensely and differentiated them from other cell types in normal reticuloendothelial tissues and lesions, but also stained smooth muscle cells and endothelial cells when these cells developed lipid vacuoles. UEA stained the endothelium of vasa vasorum consistently in human arteries, but staining of artery lumen endothelium was variable. Endothelial cells of rabbit or monkey vessels did not stain with UEA. DBA, PNA, and SBA did not consistently stain any cellular structures in arteries. PHA was found to be an excellent marker to differentiate and quantify macrophages in glutaraldehyde or formalin-fixed, paraffin-embedded experimental and human atherosclerotic lesions. Con A, RCA and WGA merit further detailed study in conjunction with other histochemical tests as possible markers of functional changes in arterial cells during lesion development.
Atherosclerosis 1986 Sep
PMID:Lectin binding to distinguish cell types in fixed atherosclerotic arteries. 353 93

Samples from 34 patients were studied both histologically and immunocytochemically by the indirect biotin-avidin peroxidase technique to analyse the distribution of the extracellular matrix components (type IV collagen, fibronectin, types I and III collagens) in dissection of the aorta. Most showed defects in type IV collagen around medial smooth muscle cells. Defects in smooth muscle cell basement membrane were found throughout the media in cystic medial degeneration and in medionecrosis, whereas in atherosclerosis such unlabelled areas were found only above advanced atherosclerotic plaques. In aortitis other defects in the smooth muscle cell basement membrane were found in areas of inflammatory infiltrates. In all of these conditions similar defects in fibronectin expression were also found. No defects in the expression of interstitial collagens type I and III were seen in the dissecting aortas. Moreover, cystic medial degeneration, medionecrosis, and atherosclerosis were characterised by intense staining of these interstitial matrix components. In the pathogenesis of the aortic dissection local changes in the basement membranes of the medial layer may be important.
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PMID:Histological pattern and changes in extracellular matrix in aortic dissections. 353 14

A histopathological and histoimmunological comparison was performed on 143 fragments on coronary arteries taken from 43 patients who died of ischemic heart disease and from 20 patients who died of other diseases. The immunological study research of Ig (A, G, M) and C3 fraction of complement in the 3 coronary layers was done by the immuno-peroxidase technique. The fixation was essentially observed in fibromyocytes. A good correlation existed between atherosclerosis lesions and fixation of Ig and C3 fraction of complement in both the media and the intima. On the other hand, this correlation was not observed in the adventitia. Accumulation of immunoglobulins and of the C3 fraction of complement in atherosclerosis seemed specific and proportional to the degree of arterial well lesion. The significance and the role of this accumulation remains to be studied. It may be hypothesized that Ig and complement fixation on fibromyocyte cell receptors or on the fibrous tissue fundamental substance is followed by the formation of antigen-antibody complexes, which act as foreign bodies which are either responsible for (or a reflection) of the onset of lesions or, at least, of their increasing severity or their persistence.
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PMID:[Presence of immunoglobulins and complement in the walls of the coronary arteries in atherosclerosis]. 353 28

The effects of different distending pressures on permeability of dog and human arteries to horseradish peroxidase (HRP) were studied. A new catheter was employed to achieve the distention of defined vessel segments to the desired pressure. Normal dog brachial arteries were studied both post mortem and in vivo. Mildly to moderately diseased human coronary arteries were studied post mortem. A predictable linear relationship between pressure and penetration of HRP into the dog arterial media was found, using pressures of 0, 150, 300 and 500 mm Hg. Postmortem vessels were consistently less permeable than those studied in vivo. Full penetration of the media by HRP was achieved by application of 300 mm Hg pressure for 45 sec with the new catheter. When human coronary lesions were examined under these same conditions, plaques were readily demonstrated to be permeable to HRP, even to a depth of many hundreds of micrometer. Thus, penetration of arterial wall thickness by HRP (Mr 40,000 dalton) is related to the distending pressure applied. Human coronary plaques also show ready penetrance by HRP. The new catheter described allows the application of these pressures to defined segments of the arterial tree.
Atherosclerosis 1987 Jun
PMID:Influence of pressure on permeability of normal and diseased muscular arteries to horseradish peroxidase. A new catheter approach. 361 87


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