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)

Patients with peripheral arterial disease (PAD) are at increased risk of generalized atherothrombotic events. Epidemiologic data shows a high rate of co-prevalence of PAD and atherosclerosis in other vascular beds. Aggressive risk-factor modification and antiplatelet therapy has become the cornerstone of treatment to prevent ischaemic events associated with PAD. Recent clinical trials have confirmed the clinical benefit of clopidogrel and ticlopidine in patients with PAD, agents that irreversibly inhibit the binding of adenosine diphosphate to its platelet receptor. In the clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE) trial, clopidogrel was associated with an overall risk reduction of 8.7% (compared with aspirin, P=0.043) in myocardial infarction (MI), ischaemic stroke and vascular death. These results demonstrated that long-term administration of clopidogrel was effective in preventing ischaemic events in patients with atherosclerotic vascular disease including PAD. Aspirin and/or clopidogrel are the antiplatelet agents of choice for the reduction of atherothrombotic events in patients with PAD.
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PMID:Preventing atherothrombotic events in peripheral arterial disease: the use of antiplatelet therapy. 1188 78

The arachidonate cascade includes the cyclooxygenase (COX) pathway to form prostanoids and the lipoxygenase (LOX) pathway to generate several oxygenated fatty acids, collectively called eicosanoids. Eicosanoids are suggested to play a dual role in regulating cell survival and apoptosis in various types of cells through an unknown mechanism. We found apoptosis in cultured Madin-Darby canine kidney (MDCK) cells treated with 12-O-tetradecanoylphorbol beta-acetate (TPA), a potent tumor promoter, and nordihydroguaiaretic acid (NDGA), a LOX inhibitor. The effect of TPA was synergistically stimulated along with NDGA. Aspirin, a COX inhibitor, was not effective. The target of NDGA might be different from the mechanism involving a LOX activity in some kinds of carcinoma cells because the increased expression of 12-LOX was not detected in MDCK cells treated with TPA. Caspase and poly(ADP-ribose) metabolites were found to be involved in the signal transduction pathway of the TPA- and NDGA-induced apoptosis in MDCK cells. Alternatively, hydrogen peroxide-induced apoptosis was not affected by NDGA. Thus, the TPA-induced response involved the mechanism independent of the oxidative stress. Obesity is a risk factor for severe diseases including noninsulin-dependent diabetes and atherosclerosis characterized by the changes of cell properties of adipocytes. We found that conjugated linolenic acid from bitter gourd was able to induce apoptosis in mouse preadipogenic 3T3-L1 cells. The findings provide the potential use of conjugated fatty acids to regulate obesity.
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PMID:Regulation of apoptosis through arachidonate cascade in mammalian cells. 1239 27

Platelets play a key role in the pathogenesis of atherosclerosis and acute coronary syndromes and antiplatelet therapy offers a clinical benefit. Although aspirin is the most widely used agent, there are several conditions in which aspirin may fail to provide a full antithrombotic benefit. Furthermore, data concerning the relationship between platelet function, aspirin, and the associated risk factors are limited. In the present study. ADP and collagen-induced platelet aggregation of 200 consecutive patients with suspected coronary artery disease (CAD) who underwent coronary angiography were evaluated. The patients were classified into three groups according to the number of stenotic vessels. One hundred and eight patients were using 300 mg/day of aspirin. The associated cardiovascular risk factors were also considered. The collagen-induced platelet aggregation of smokers was significantly higher than non-smokers (P < 0.05). Although platelet aggregation was higher in diabetic and hypertensive patients, the difference was not statistically significant. No significant correlation was found between platelet aggregation and other risk factors. The collagen-induced platelet aggregation of the subjects with non-stenotic vessels was reduced by aspirin (P < 0.05). Aspirin did not sufficiently inhibit ADP and collagen-induced aggregation in patients with CAD. This finding supports the idea that the nonplatelet-mediated effects of aspirin could be more important than its antiplatelet effect in clinical use and the use of new potent antiplatelet drugs may complete its antiplatelet effect.
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PMID:Differential effect of aspirin on platelet aggregation in patients with coronary artery disease in relation with associated risk factors. 1262 34

Ischemic heart disease (IHD) represents a pathophysiologic continuum consisting of stable angina, unstable angina, non-ST-segment elevation myocardial infarction, and ST-segment elevation myocardial infarction. Patients who develop a change in their usual stable pattern of ischemia are classified as having an acute coronary syndrome, which includes patients with unstable angina, non-ST-segment elevation myocardial infarction, and ST-segment elevation myocardial infarction. Such progression from a stable to an unstable state is believed to result from disruption of an atherosclerotic plaque with subsequent platelet aggregation and thrombus formation. This, in turn, leads to the clinical manifestations of unstable angina, MI or death. Because platelets play a central role in the thrombotic complications of atherosclerosis, antiplatelet agents have been the cornerstone of the therapy for IHD. Aspirin has been the traditional antiplatelet agent, and remains the mainstay of treatment for all forms of IHD. However, aspirin is a weak antiplatelet agent and is often poorly tolerated by many patients. Clopidogrel is a new antiplatelet agent of the thienopyridine class. Clopidogrel, when used alone, and especially in combination with aspirin, has been shown to improve outcomes in patients with IHD across a variety of syndromes. However, combination therapy with aspirin and clopidogrel has been associated with an increased risk of bleeding. Therefore, despite improved outcomes, further studies are required to determine the optimal duration and dosage regimen of such combination therapy to maximize its risk-benefit ratio.
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PMID:Clopidogrel in the management of ischemic heart disease. 1271 81

Infection with Chlamydia pneumoniae has been implicated as a potential risk factor for atherosclerosis. This study was designed to investigate the mechanisms of the anti-chlamydial activity of aspirin. A reporter gene assay for NF-kappa B activity, immunoblot analysis for cyclo-oxygenase (COX)-2 and radioimmunoassay for prostaglandin E(2) (PGE(2)) were performed. Following infection of HEp-2 cells with C. pneumoniae, NF-kappa B was activated, COX-2 was induced and PGE(2) was elevated. Aspirin inhibited NF-kappa B activation at a concentration of 0.1 mM, partially inhibited COX-2 induction and blocked PGE(2) synthesis completely. In addition, high doses of aspirin (1 and 2 mM) inhibited chlamydial growth in HEp-2 cells, decreasing the number and size of inclusion bodies; this effect could be overcome by adding tryptophan to the culture. Indomethacin also blocked the synthesis of PGE(2), but had no effect on COX-2 expression or chlamydial growth. These results indicate that aspirin not only has an anti-inflammatory activity through prevention of NF-kappa B activation but also has anti-chlamydial activity at high doses, possibly through depletion of tryptophan in HEp-2 cells.
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PMID:Aspirin inhibits Chlamydia pneumoniae-induced NF-kappa B activation, cyclo-oxygenase-2 expression and prostaglandin E2 synthesis and attenuates chlamydial growth. 1272 17

Accelerated atherosclerosis and the increased risk of thrombotic vascular events in diabetes may result from dyslipidemia, endothelial dysfunction, platelet hyperreactivity, an impaired fibrinolytic balance, and abnormal blood flow. There is also a correlation between hyperglycemia and cardiovascular (CV) events. The importance of platelets in the atherothrombotic process has led to investigation of using antiplatelet agents to reduce CV risk. A meta-analysis conducted by the Antiplatelet Trialists' Collaboration demonstrated that aspirin reduced the risk of ischemic vascular events as a secondary prevention strategy in numerous high-risk groups, including patients with diabetes. Based on results from placebo-controlled randomized trials, the American Diabetes Association recommends low-dose enteric-coated aspirin as a primary prevention strategy for people with diabetes at high risk for CV events. Clopidogrel is recommended if aspirin allergy is present. There is occasionally a need for an alternative to aspirin or for additive antiplatelet therapy. Aspirin in low doses inhibits thromboxane production by platelets but has little to no effect on other sites of platelet reactivity. Agents such as ticlopidine and clopidogrel inhibit ADP-induced platelet activation, whereas the platelet glycoprotein (Gp) IIb/IIIa complex receptor antagonists block activity at the fibrinogen binding site on the platelet. These agents appear to be useful in acute coronary syndromes (ACSs) in diabetic and nondiabetic patients. A combination of clopidogrel plus aspirin was more effective than placebo plus standard therapy (including aspirin) in reducing a composite CV outcome in patients with unstable angina and non-ST segment elevation myocardial infarction. In a meta-analysis of six trials in diabetic patients with ACSs, intravenous GpIIb-IIIa inhibitors reduced 30-day mortality when compared with control subjects. Results from controlled prospective clinical trials justify the use of enteric-coated low-dose aspirin (81-325 mg) as a primary or secondary prevention strategy in adult diabetic individuals (aged >30 years) at high risk for CV events. Recent studies support the use of clopidogrel in addition to standard therapy, as well as the use of GpIIb-IIIa inhibitors in ACS patients.
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PMID:The platelet in diabetes: focus on prevention of ischemic events. 1283 32

1. Atherosclerotic cardio- and cerebrovascular disease is a leading cause of mortality in Western countries. Aspirin-like drugs are widely used to prevent and treat these occlusive cardio- and cerebrovascular diseases. The beneficial effects of these drugs have been largely attributed to inhibition of platelet cyclo-oxygenase activity and thromboxane (TX) A2 production. We investigated the effect of an aspirin-like drug, namely indomethacin, on endothelial function, plaque and platelet aggregation and the formation of vasoactive substances during the development of atherosclerosis in cholesterol-fed rabbits. 2. Rabbits were fed 1% cholesterol (n = 8), 1% cholesterol plus 25 mg/day indomethacin (n = 8) or normal rabbit chow (control group; n = 8) for 12 weeks. Urinary excretion rates of 2,3-dinor-TXB2, 6-keto-prostaglandin (PG) F1alpha, 8-iso-PGF2alpha and nitrate were analysed at the beginning of dietary intervention and at 4 weekly intervals thereafter. At the end of the study period, platelet aggregation, aortic plaque formation and endothelium-dependent and -independent vascular functions of isolated aortic rings ex vivo were assessed. 3. Compared with control, in the cholesterol-fed group, urinary 2,3-dinor-TXB2, 6-keto-PGF1alpha and 8-iso-PGF2alpha excretion and platelet aggregation were significantly increased (P < 0.05), but urinary excretion of nitrate was decreased (P < 0.05). Treatment with indomethacin significantly reduced platelet aggregation, urinary 2,3-dinor-TXB2, 6-keto-PGF1alpha and 8-iso-PGF2alpha excretion (P < 0.05 vs the cholesterol-fed group) and attenuated the reduction in urinary nitrate excretion. 4. Cholesterol feeding progressively increased aortic intimal thickening and impaired endothelium-dependent vasodilator function (P < 0.05 vs control), whereas indomethacin partially prevented aortic plaque formation and restored endothelium-dependent vasodilation (P < 0.05 vs the cholesterol-fed group). 5. The present study demonstrates that indomethacin reduces the progression of atherosclerotic lesions and improves endothelium-mediated vascular responses ex vivo in cholesterol-fed rabbits. The beneficial effects of indomethacin may be due to its ability to prevent the elevation of platelet aggregation, TXA2 (measured as urinary 2,3-dinor-TXB2 excretion) and 8-iso-PGF2alpha formation and to retard the decrease in endogenous nitric oxide synthesis (assessed as urinary excretion of nitrate). Despite indomethacin treatment leading to the suppression of prostacyclin biosynthesis (assessed as urinary 6-keto-PGF1alpha excretion), according to our data, indomethacin appears to preserve endothelial function.
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PMID:Improvement of vascular function by chronic administration of a cyclo-oxygenase inhibitor in cholesterol-fed rabbits. 1285 34

Statins, aspirin and angiotensin II modulators (A II-M: angiotensin-converting enzyme (ACE) inhibitors and angiotensin II type I receptor blockades) may have an anti-inflammatory effect, but the relationship between the effects of statins, aspirin and A II-M on high-sensitive C-reactive protein (hs-CRP) levels remains to be determined. We examined serum hs-CRP levels in consecutive patients with stable ischemic heart disease (IHD) (n=1231; 65+/-9 years; male/female, 927/304) and without IHD (n=226; 64+/-9 years; male/female, 117/109). Blood samples were collected on the day of catheterization. The hs-CRP levels were significantly higher in the IHD than in the non-IHD patients (0.32+/-0.52 vs. 0.24+/-0.29 mg/dl, P<0.05). Treatment with statins was associated with significantly lower hs-CRP levels in both groups (non-IHD, 0.17+/-0.14 vs. 0.26+/-0.31 mg/dl; IHD, 0.27+/-0.34 vs. 0.35+/-0.59 mg/dl; both P<0.05). hs-CRP levels were significantly lower only in IHD patients treated with A II-M than in those not treated with A II-M (0.28+/-0.34 vs. 0.34+/-0.58 mg/dl, P<0.05). Aspirin did not have any effect on the hs-CRP level in either group. The hs-CRP levels were significantly lower in IHD patients treated with statins and/or A II-M than those treated with neither statins nor A II-M (statin+/A II-M+, 0.28+/-0.29 mg/dl; statin+/A II-M-, 0.26+/-0.36 mg/dl; statin-/A II-M+, 0.28+/-0.37 mg/dl; statin-/A II-M-, 0.38+/-0.66 mg/dl; P<0.01). These results indicate that statins and A II-M, but not aspirin, in commonly used doses have an anti-inflammatory action as assessed by measurement of CRP levels in IHD patients.
Atherosclerosis 2003 Jul
PMID:Relationship between effects of statins, aspirin and angiotensin II modulators on high-sensitive C-reactive protein levels. 1286 Feb 62

Carotid atherosclerosis is one of the main risk factors for ischemic stroke. The annual risk of ipsilateral stroke for asymptomatic, albeit severe stenoses is as low as 1 to 2%, but increases to 13% in patients with recent ischemic symptoms. However the risk decreases after the first 2-3 years from the symptomatic episode, dropping to 3%. Echo-color Doppler ultrasonography is the screening method of choice, being highly accurate, noninvasive and low-cost. Carotid angiography still represents the gold standard, however, less invasive techniques as RM angiography and Angio-CT are becoming increasingly common. Based on NASCET, ECST and ACAS results, carotid endarterectomy (CE) is strongly recommended for severe symptomatic stenoses, while for the moderate symptomatic and the severe asymptomatic ones the benefit in terms of stroke risk reduction is modest and surgery should be restricted to selected cases in surgical centers of high experience. For severe asymptomatic stenoses NNT is too high to recommend indiscriminate surgery; we are waiting for the results of ACSRS trial, designed to identify a subset of patients at risk of ipsilateral stroke greater than 4%/y, that may be considered for CE, while patients at low risk will be spared from unnecessary operation. Apart from surgery, in all patients with carotid atherosclerosis correction of cardiovascular risk factors is mandatory. Antiplatelet therapy (ASA alone or with dypiridamole, ticlopidine) is effective in secondary prophylaxis of athero-thrombotic stroke; its use in asymptomatic carotid stenoses can be recommended, even if more because of a plausible rationale than of clinical trial-based evidences.
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PMID:Management of patients with carotid stenosis. 1367 81

During accelerated vascular remodeling such as in atherosclerosis, the composition of the extracellular matrix becomes altered. The matrix components of the diseased artery influence cellular processes such as adhesion, migration and proliferation. Furthermore, in atherosclerosis, the inability of the cells within the lesion to produce a mechanically stable matrix may lead to plaque rupture. In this immunohistochemical study of atherosclerotic mice aorta, we have reviewed the presence of ECM components with roles in maintaining tissue structure and function. These components include osteopontin and COMP as well as the leucine rich repeats proteins decorin, PRELP, and fibromodulin. Immunohistochemistry demonstrated presence of osteopontin, COMP, decorin, PRELP and fibromodulin in lesion areas of ApoE/LDLr deficient mice. Some advanced lesions exhibited areas of cartilage-like morphology and were shown to represent cartilage by their content of the cartilage specific proteins collagen II and aggrecan. The results suggest that cartilage-associated cell/collagen binding ECM proteins may be involved in the pathogenesis of atherosclerosis.
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PMID:Extracellular matrix components in atherosclerotic arteries of Apo E/LDL receptor deficient mice: an immunohistochemical study. 1502 95


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