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)

Favorable changes in lipoproteins, inhibition of platelet aggregation, reduction of serum thromboxane (TX), altered plasma-membrane fluidity, and reduced production of growth factors (mitogens) have all been implicated as possibly being involved in the inhibition of arteriosclerosis by fish oil (FO), which is rich in omega 3 fatty acids; however, causal relations are mostly lacking. Several putative mechanisms responsible for the salutary effects of FO were investigated in a canine model of accelerated vein-graft arteriosclerosis. Venoarterial autografts (N = 192) were implanted in 48 hypercholesterolemic dogs divided into six groups: group A, control; B, FO (as MaxEPA, 200 mg/kg/day eicosapentaenoic acid); C, aspirin (ASA, 50 mg/kg/day); D, TX synthetase inhibitor (TXSI [CGS-12970], 10 mg/kg/day); E, FO + ASA; and F, FO + TXSI. At sacrifice 3 months later, there was no significant difference in plasma lipoproteins, hepatic low density lipoprotein-receptor concentration, red blood cell fragility, bleeding time, or platelet count compared with controls; the decrease in platelet aggregation (30 +/- 5% [mean +/- SEM]) was similar in all treatment groups. Arterialized vein-graft intimal thickening was significantly inhibited by FO (with or without ASA), while ASA alone was ineffective. Conversely, serum TX was significantly lower only in the ASA and FO + ASA groups. Serum mitogenic activity was higher at 3 months in the control group versus all treatment groups. Compared with baseline values, serum mitogenic activity rose significantly over time in the control and the TXSI groups, and an increase or rising trend was present in all other treatment groups except for the FO-treated animals. Thus, the salutary biologic effect of FO in this hypercholesterolemic model of arterialized vein grafts may have been more related to in vivo inhibition of platelet-mitogen growth factor release than to changes in lipoproteins, low density lipoprotein receptors, platelet function, or eicosanoid metabolism. These observations underscore the need for further studies to clarify the interactions between FO (omega 3 fatty acids) and paracrine cellular mitogenic factors in the context of atherosclerosis prevention.
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PMID:Mechanisms responsible for inhibition of vein-graft arteriosclerosis by fish oil. 276 20

Platelets are believed to play a role in the pathogenesis of atherosclerosis and of the vascular obstruction that causes the acute complications of coronary artery disease. Since specific behavioral patterns appear to be related to the development of coronary artery disease and since emotional stress may predispose an individual to acute cardiovascular ischemia, it was hypothesized that platelet activation by catecholamines might be involved in these events. To study emotional stress, plasma samples were obtained from 61 senior medical residents immediately before they were to speak in public. There were significant increases in the plasma concentrations of the platelet-secreted proteins platelet factor 4 and beta-thromboglobulin and epinephrine and norepinephrine immediately before speaking, which demonstrates that platelet activation and secretion occur in association with this type of emotional stress. Four trials were carried out to study the mechanism for this observed platelet secretion: (1) phenoxybenzamine, (2) propranolol, (3) 650 mg aspirin, and (4) 80 mg aspirin were given several hours before the public speaking engagement. Neither phenoxybenzamine nor propranolol in doses that blocked the hemodynamic effects of alpha 1- and beta 1-adrenergic stimulation modified platelet secretion. Aspirin also did not block platelet secretion, which suggests that platelets were not being stimulated through a cyclooxygenase-dependent pathway. This study provides direct evidence of platelet secretion in vivo in association with emotional stress, and underscores the potential importance of platelet activation and secretion in the acute events that occur in patients with vascular disease.
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PMID:Platelet activation and secretion associated with emotional stress. 298 76

A method was developed for the noninvasive insertion of a vascular ring prostheses aimed at preserving arterial patency and preventing restenosis following angioplasty. Using a specially designed 7F catheter 22 nitinol (TiNi) wire prostheses (I.D. 5 mm; 0.25 mm thickness) were torsion reduced in diameter and inserted under fluoroscopy into both carotid (n = 2) and iliac-femoral arteries (n = 20) of dogs. Aspirin (650 mg BID) and Persantin (200 mg BID) were given for only 30 days postoperatively. Angiography of all rings at 1, 6, 12 months exhibited excellent biocompatibility and long term patency 91% (20/22) as reported in Trans ASAIO 32:30, 1986. Four rings inserted in the right and left common iliac arteries and femoral artery were followed for up to 2 years and exhibited 100% patency. Angiography demonstrated that the anchorage of the prostheses was stable and the lumen was uniformly covered by a thin neointimal layer of endothelial like cells. The prostheses were patent with no evidence of thrombosis or inflammation. In view of the problem of recurrent stenosis occurring during the healing period after balloon angioplasty (PTA or PTCA), this approach may lead to a new means of clinical intervention in atherosclerosis.
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PMID:Biological performance of TiNi shape memory alloy vascular ring prostheses: a two year study. 320 77

Derivatives of arachidonic acid may be involved in atherosclerosis and its clinical complications. There is much interest in pharmacologically manipulating the arachidonic acid cascade as a means of preventing cardiovascular disease. The development of atherosclerosis has been intensively studied and the consequences of cardiovascular or cerebrovascular vessel occlusion are too familiar. Many factors are probably involved, but the role of plasma lipoproteins and the interactions between various constituents of blood and blood vessel walls have received particular attention. The risk of cardiovascular disease associated with high plasma concentrations of the low density lipoproteins and the possible protective effects of high density lipoproteins have been well documented. Much is now known about lipoprotein biochemistry, and the importance of controlling the quantity and quality of dietary lipids has been demonstrated in epidemiological studies. In studies of patients with transient ischaemic attacks, aspirin reduced the risk of stroke and death in males, although these benefits were not as convincingly demonstrated in women. The majority of patients were given aspirin 1300 mg daily, but the optimum dosage was not properly evaluated. Administering aspirin in combination with another antiplatelet drug did not appear to offer any therapeutic advantage in these patients. Aspirin showed a positive, but non-significant trend towards reduced numbers of cardiac events, non-fatal infarcts and total mortality in patients who had experienced at least one myocardial infarction. In contrast, statistically significant beneficial effects were recorded when patients with unstable angina were administered aspirin. The risks of myocardial infarction or coronary death were reduced by 51% in 2 large studies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of arachidonic acid metabolites in cardiovascular homeostasis. Biochemical, histological and clinical cardiovascular effects of non-steroidal anti-inflammatory drugs and their interactions with cardiovascular drugs. 329 23

Cholesterol oxidation products (oxysterols) found in foods may be atherogenic, possibly by altering the barrier function of the vascular endothelium. To investigate this hypothesis, endothelial cells were cultured on micropore filters and the effect of cholesterol and the oxysterol cholestan-3 beta,5 alpha,6 beta-triol (Triol) on albumin transfer across cultured vascular endothelial monolayers (ECM) was studied. Exposure to Triol significantly increased albumin transfer across ECM. The effect of Triol on endothelial cell barrier function was time and concentration dependent, with maximum albumin transfer being reached at 20 microM Triol and after a 24-h exposure. Pure cholesterol, on the other hand, did not affect albumin transfer at concentrations as high as 130 microM. Although an increase in albumin transfer across ECM was observed after a 2-h incubation with Triol-enriched media, a 24-h incubation period was necessary to cause a significant release of cellular lactate dehydrogenase (LDH) into the culture media. Morphological perturbations of the cell monolayers were observed at approx. 14-18 h after cell exposure to Triol-enriched media. Enrichment with cholesterol or vitamin E did not prevent the Triol-induced increase in albumin transfer across ECM. These results suggest that exposure to oxidized cholesterol, but not cholesterol, itself, reduces the ability of the endothelium to act as a selectively permeable barrier to plasma components, and that these events may not be prevented by cholesterol or vitamin E.
Atherosclerosis 1987 Dec
PMID:Cholestan-3 beta,5 alpha,6 beta-triol decreases barrier function of cultured endothelial cell monolayers. 342 58

In this review, the major current problems related to the pharmacology and clinical use of antiplatelet drugs are discussed in relation to the physiopathology of the platelet-vessel wall interaction and arterial thrombus formation. Although platelet adhesion to injured vessels is a crucial step in thrombogenesis, none of the currently used antiaggregating drugs prevents this phenomenon. Why the normal endothelium does not react with platelets is not known. Thus we are unable to pharmacologically restore endothelial 'non-thrombogenicity' when lost by single or repeated injury. In contrast, more information is available on the mechanisms controlling and amplifying platelet activation by physiological stimuli (such as collagen and thrombin), and on their pharmacological modulation. The 3 main amplification loops involve arachidonic acid metabolism, ADP release and possibly the availability of a phospholipid platelet activating factor. These pathways are in turn activated by the phosphatidylinositol cycle. The most widely used antiaggregating drug is aspirin. It prevents the formation of arachidonic acid metabolites both in platelets and in vascular cells. The use of low-dose aspirin, thromboxane-synthase inhibitors, thromboxane receptor antagonists, epoprostenol (prostacyclin) and its stable analogues, and ticlopidine all appear to be promising pharmacological approaches, but none has so far been tested in clinical trials for thrombosis prevention. On the other hand, aspirin (in relatively large doses of 300 to 1500 mg daily), sulphinpyrazone and dipyridamole have been tested alone or in combination in the secondary prevention of thromboembolic complications. Aspirin has significantly reduced both the occurrence of myocardial infarction and mortality rate in patients with unstable angina and/or previous myocardial infarction; it has also proved beneficial in cerebrovascular disease. The beneficial effect of aspirin was dose-independent. In some of these trials aspirin was combined with either dipyridamole or sulphinpyrazone. When used alone, the latter compound has reduced sudden death or thromboembolic complications in patients with myocardial infarction. It remains to be established whether antiplatelet therapy may prevent or stop the progression of atherosclerosis.
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PMID:Current issues in thrombosis prevention with antiplatelet drugs. 352 85

The effect of aspirin on the development of hypercoagulability in the penile blood during erection was studied in five Chacma baboons. Aspirin prevented the generation of hypercoagulability and may be of importance in delaying the development of penile atherosclerosis and ageing impotence.
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PMID:Effect of single dose aspirin on the development of penile hypercoagulability during erection. 356 91

Lesions of vascular human EC play an important role in the development of thrombi and atherosclerosis. The factors which control the repair of vascular lesions are not well known. In addition, they are difficult to study because vascular EC from large vessels are fastidious cells to grow in tissue culture. We have investigated some of the factors that may be important in human umbilical vein EC growth in primary culture. Because of reported species differences in EC culture, we have decided to culture human EC only in the presence of biological culture reagents of human origin. Human umbilical vein EC, at low seed density, can be grown to confluency on a human FN matrix or on human ECM providing the medium is supplemented with a high concentration (30%) of human serum. The optimal proliferation of EC (even when seeded at clonal density) is obtained if HBE is added. HBE cannot completely replace serum, but EC proliferate to a similar extent whether they are grown on FN or on ECM in the presence of 30% human serum of 10% human serum plus HBE. Thus, HBE contains a growth factor activity for human EC which stimulates cell growth and DNA replication. Further work is needed to purify HBE and to compare it to other endothelial cell growth factors isolated from bovine brain and bovine eye.
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PMID:Effects of an extract of human brain containing growth factor activity on the proliferation of human vascular endothelial cells in primary culture. 624 86

Large-scale clinical trials of the use of aspirin in post-myocardial infarction patients were based on the assumption that inhibition of platelet activity would reduce thromboembolism associated with atherosclerosis, and that thromboembolism is a major cause of the clinical complications of atherosclerosis. However, spasm and occlusive thrombi may also contribute to this picture, and thus thromboembolism is probably only one of the mechanisms that cause the clinical complications. Aspirin inhibits thrombosis only if thromboxane A2 formation by platelets plays a major part in the growth of thrombi; aspirin has little effect on thrombosis when thrombin generation and fibrin formation are dominant factors. Nevertheless, analysis of the combined data from the six clinical trials indicates a highly significant (21 percent) reduction in reinfarction rate and a 16 percent reduction in cardiovascular mortality rate in patients treated with aspirin. Aspirin may be most useful in treating an as-yet-unidentified subgroup of patients.
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PMID:Aspirin in the treatment of cardiovascular disease: a review. 640 10

Primary cultures of confluent human endothelial cells (ECM) were grown in media containing the major lipoproteins (LP) and lipoprotein deficient serum (LDS). The release of 6-keto-PGF1 alpha, von Willebrand factor (VIII RAg) and apolipoproteins (apo) A-I and A-II were investigated by radioimmunoassay. The cell-associated VIII RAg, apo A-I and apo A-II were also confirmed by fluorescein antibodies, and the synthesis of the apolipoproteins was examined by incorporation of [3H]leucine. Apo A-I and apo A-II were located and synthesized in ECM, yet only apo A-I was released into the medium. Very low density (VLDL) and low density lipoproteins (LDL) in concentrations of 50-600 micrograms/ml stimulated release of apo A-I. Stimulation of ECM for 5 min with thrombin (T) or arachidonic acid (A) did not induce apo A-I release. VIII RAg was always released into the media from ECM. The release was not affected by the lipoproteins. VIII RAg was also localized on the cell surface (VIII RAgC) and approximately 80% was released by trypsin. LDL stimulated the occurrence of factor VIII RAg on the cell surface. 6-Keto PGF1 alpha was always released into the medium and the production was stimulated by T and AA. The main lipoproteins (50-600 micrograms/ml) and apo A-I and A-II did not affect the release of 6-keto-PGF1 alpha. This study shows that endothelial cells synthesize and release proteins important for thrombogenesis and atherosclerosis. The release of apolipoproteins A-I was stimulated by VLDL and LDL, and the concentration of cell-related factor VIII RAg was stimulated by LDL.
Atherosclerosis 1984 Mar
PMID:The effect of lipoproteins on the synthesis of prostacyclin, von Willebrand factor and apolipoproteins A-I and A-II in cultured human endothelial cells. 642 92


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