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 acute coronary syndromes arise from procoagulant changes in complex plaques, which trigger both platelet activation and coagulation pathways. These 2 pathways intersect at a number of points that form positive-feedback loops to sustain and accelerate thrombus formation. In normal hemostasis and with a healthy endothelium, intravascular thrombosis is prevented, and vascular patency is protected by the fibrinolytic system and a number of antithrombotic factors, such as antithrombin, thrombomodulin, and tissue factor pathway inhibitor. However, atherosclerosis is characterized by a hypercoagulable state, and the fibrinolytic balance is skewed toward occlusive thrombus formation at critical sites on vulnerable plaques. This review focuses on cellular and humoral mechanisms and the antithrombotic strategies that are important during the acute phase of an ischemic coronary syndrome, both in patients managed conservatively and in patients scheduled for an interventional procedure. These strategies include fibrinolytic therapy, antiplatelet therapies (aspirin, clopidogrel, glycoprotein IIb/IIIa receptor inhibitors), and low-molecular-weight heparin.
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PMID:Prothrombotic and antithrombotic pathways in acute coronary syndromes. 1281 29

Platelet aggregation plays a key role in the development of complications of atherosclerosis. By inhibiting platelet aggregation in a pharmacological way complications such as myocardial infarction and sudden death may be prevented. This goes for primary as well as secondary prevention. The most relevant substances for this goal are aspirin, clopidogrel and the new glycoprotein IIb/IIIa inhibitors.
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PMID:Platelet aggregation inhibitors in prevention and treatment of coronary thrombosis. 1294 62

We report a 64-year-old Turkish man who presented with unstable angina pectoris. Coronary angiography revealed massive intracoronary thrombus, which completely occluded the distal part of the left circumflex coronary artery. The thrombotic segment and the rest of the coronary tree were free of atherosclerosis. The patient was treated with intravenous tirofiban, a glycoprotein IIb/IIIa inhibitor. A control angiography was performed one week later and showed total dissolution of the thrombus with tirofiban therapy.
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PMID:Treatment of intracoronary thrombus using tirofiban in a patient with normal coronary arteries. 1509 Jul 12

Several genes are regulated by tocopherols which can be categorized, based on their function, into five groups: genes that are involved in the uptake and degradation of tocopherols (Group 1) include alpha-tocopherol transfer protein (alpha-TTP) and cytochrome P450 (CYP3A); genes that are associated with lipid uptake and atherosclerosis (Group 2) include CD36, SR-BI and SR-AI/II. Genes that modulate the expression of extracellular proteins (Group 3) include tropomyosin, collagen(alpha1), MMP-1, MMP-19 and connective tissue growth factor (CTGF). Genes that are related to inflammation, cell adhesion and platelet aggregation (Group 4) include E-selectin, ICAM-1, integrins, glycoprotein IIb, II-2, IL-4 and IL-beta. Group 5 comprises genes coding for proteins involved in cell signaling and cell cycle regulation and consists of PPAR-gamma, cyclin D1, cyclin E, Bcl2-L1, p27 and CD95 (Apo-1/Fas ligand). The expression of P27, Bcl2, alpha-TTP, CYP3A, tropomyosin, II-2, PPAR-gamma, and CTGF appears to be up-regulated by one or more tocopherols whereas all other listed genes are down-regulated. Several mechanisms may underlie tocopherol-dependent gene regulation. In some cases protein kinase C has been implicated due to its deactivation by alpha-tocopherol and its participation in the regulation of a number of transcription factors (NF-kappaB, AP-1). In other cases a direct involvement of PXR/RXR has been documented. The antioxidant responsive element (ARE) appears in some cases to be involved as well as the transforming growth factor beta responsive element (TGF-beta-RE). This heterogeneity of mediators of tocopherol action suggests the need of a common element that could be a receptor or a co-receptor, able to interact with tocopherol and with transcription factors directed toward specific regions of promoter sequences of sensitive genes. Here we review recent results of the search for molecular mechanisms underpinning the central signaling mechanism.
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PMID:Regulation of gene expression by alpha-tocopherol. 1531 6

The acute coronary syndromes (ACS), consisting of ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), and unstable angina, remain a leading cause of death in the United States. Through the process of atherothrombosis, underlying atherosclerosis can progress to an acute ischemic coronary event. This disease mechanism is also common to ischemic stroke and peripheral arterial disease. As ACS is a heterogeneous disease, accurate patient diagnosis and risk categorization is essential. Treatment approaches for both STEMI and NSTEMI ACS consist of a combination of surgical intervention and pharmacotherapy, with antiplatelet agents such as clopidogrel, aspirin and glycoprotein IIb/IIIa receptor antagonists playing an essential role.
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PMID:Role of antiplatelet therapy in cardiovascular disease I: Acute coronary syndromes. 1553 83

Advances in percutaneous coronary revascularization have meant that, increasingly, patients with multivessel diseases are initially treated with the methods of interventional cardiology. Ongoing studies involving new stent coatings and optimized anti-thrombotic therapies could help to lower future restenosis rates and improve the success rate of stenting. Thrombocyte glycoprotein IIb/IIIa receptor blockers have already been shown to reduce the rate of acute PTCA complications in high-risk patients and could have a sustained impact on the long-term prognoses for PTCA patients. However, for diabetic patients with coronary multivessel diseases, coronary artery bypass grafting using arterial grafts as the initial revascularization method must be given preference over other therapy methods. Consequently, this group of patients is bound to grow in importance in cardiac surgery. The advances made in percutaneous coronary revascularization and in coronary surgery call for further prospective, controlled, randomized clinical studies in order to establish the best possible treatment strategy for patients with diabetes. It should be noted, however, that the therapeutic effect of myocardial revascularization is generally limited to individual coronary-arterial segments, whereas the pathological process of atherosclerosis is rather diffuse. The surgical strategy should therefore be seen as part of an overall strategy which encompasses other forms of treatment (e.g. intensive efforts to improve control of blood glucose level, blood pressure, and cholesterol level) in order to arrest the general progression of the disease and to reduce the risk of myocardial infarction and death.
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PMID:Diabetes mellitus in coronary artery surgery: therapeutic strategies in the light of recent studies. 1557 76

alpha-Tocopherol modulates two major signal transduction pathways centered on protein kinase C and phosphatidylinositol 3-kinase. Changes in the activity of these key kinases are associated with changes in cell proliferation, platelet aggregation, and NADPH-oxidase activation. Several genes are also regulated by tocopherols partly because of the effects of tocopherol on these two kinases, but also independently of them. These genes can be divided in five groups: Group 1. Genes that are involved in the uptake and degradation of tocopherols: alpha-tocopherol transfer protein, cytochrome P450 (CYP3A), gamma-glutamyl-cysteine synthetase heavy subunit, and glutathione-S-transferase. Group 2. Genes that are implicated with lipid uptake and atherosclerosis: CD36, SR-BI, and SR-AI/II. Group 3. Genes that are involved in the modulation of extracellular proteins: tropomyosin, collagen-alpha-1, MMP-1, MMP-19, and connective tissue growth factor. Group 4. Genes that are connected to adhesion and inflammation: E-selectin, ICAM-1 integrins, glycoprotein IIb, IL-2, IL-4, IL-1b, and transforming growth factor-beta (TGF-beta). Group 5. Genes implicated in cell signaling and cell cycle regulation: PPAR-gamma, cyclin D1, cyclin E, Bcl2-L1, p27, CD95 (APO-1/Fas ligand), and 5a-steroid reductase type 1. The transcription of p27, Bcl2, alpha-tocopherol transfer protein, cytochrome P450 (CYP3A), gamma-glutamyl-cysteine sythetase heavy subunit, tropomyosin, IL-2, and CTGF appears to be upregulated by one or more tocopherols. All the other listed genes are downregulated. Gene regulation by tocopherols has been associated with protein kinase C because of its deactivation by alpha-tocopherol and its contribution in the regulation of a number of transcription factors (NF-kappaB, AP1). A direct participation of the pregnane X receptor (PXR) / retinoid X receptor (RXR) has been also shown. The antioxidant-responsive element (ARE) and the TGF-beta-responsive element (TGF-beta-RE) appear in some cases to be implicated as well.
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PMID:Vitamin E mediates cell signaling and regulation of gene expression. 1575 36

All stages of atherosclerotic plaques are characterized by an inflammatory component, in which T lymphocytes and macrophages orchestrate lesion progression and destabilization by releasing cytokines (e.g., interferon-gamma, tumor necrosis factor-alpha, tissue factor). At the extreme end of this process plaque rupture occurs, which may manifest clinically as an acute coronary syndrome. Hence, measuring this atherosclerosis-inherent inflammation may help predicting cardiovascular events. Accordingly, different soluble inflammatory markers were studied for their predictive value in acute coronary syndromes. Special attention was paid to high-sensitivity C-reactive protein (hs-CRP) and soluble CD40 ligand (sCD40L). The latter seems not only to be a marker of inflammation and platelet activation, but is suggested to directly destabilize atherosclerotic plaques by stimulating pro-inflammatory T lymphocytes. Therefore, reduction of soluble inflammatory markers is an attractive target for future therapeutic strategies. Statins and glycoprotein IIb/IIIa antagonists, well-established treatments in acute coronary syndromes, were demonstrated to decrease hs-CRP and sCD40L. Whether this reduction translates into a better prognosis has to be investigated in further studies.
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PMID:[The role of inflammation in the pathophysiology of acute coronary syndromes]. 1609 70

The coronary microcirculation does not only control perfusion of the myocardium, but also plays an important role for the manifestation of ischemic heart disease throughout all stages of the disease. Risk factors for coronary artery disease are associated with a reduced endothelium-dependent blood flow regulation, which not only may aggravate myocardial ischemia but also determines blood flow-induced shear stress exposed to the vascular wall, modulating the vascular milieu (e. g., by controlling nitric oxide bioactivity) and thereby altering progression of atherosclerosis in conductance vessels. Furthermore, generally impaired microvascular function is predictive of cardiovascular events, e. g., after percutaneous coronary interventions or after an acute myocardial infarction. In the latter case, thrombotic embolism from ruptured plaques in the conductance vessels as well as inflammation and reperfusion injury are the essential components of the microvascular disorder. Interestingly, therapeutic strategies which improve microvascular dysfunction, such as statins in stable coronary artery disease or glycoprotein IIb/IIIa inhibitors during acute myocardial infarction, are associated with an improved long-term prognosis. These facts give promise for new therapeutic principles: experimental data demonstrate, that the therapeutic application of stem or progenitor cells after an acute myocardial infarction induces growth of new microvessels (neovascularization) and thereby improves microvascular perfusion, which may favorably alter infarct expansion and remodeling. First clinical data, demonstrating indeed an improved coronary blood flow regulation after progenitor cell therapy in patients with ischemic heart disease, have to be established by further clinical trials.
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PMID:[Coronary microcirculation. Pathophysiology, clinical relevance, and importance for regenerative therapy after myocardial infarction]. 1633 92

Platelets are believed to play a part in all stages of the pathogenesis of ischemic stroke, from the initial formation of the atherosclerotic plaque, through plaque destabilization to the development of neuronal cell death. A process common to all of these pathogenic changes is the ability of the activated platelet to adhere to the site of disease. In addition, the release of the membrane vesicles from platelets enhances many of these processes. Therefore, an understanding of platelet adhesion and platelet microparticle release can aid the development toward the treatment and prevention of stroke. There has been much research into interventions that can reduce platelet activation in atherosclerosis and stroke. The benefits of nonpharmacologic interventions in stroke, such as diet and lifestyle modification, may in part be mediated by their effects on platelet activation. In addition, the antiplatelet drug aspirin has been shown to be useful in both the treatment of acute stroke and the secondary prevention of atherothrombosis. Other antiplatelet agents, such as the glycoprotein IIb/IIIa inhibitors and triflusal, are currently being evaluated for the treatment of acute atherothrombotic stroke.
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PMID:Platelet microparticles and platelet adhesion: therapeutic implications for the prevention and treatment of stroke. 1663 45


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