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)

Atherosclerosis is a chronic inflammatory disease accompanied by the expression of endothelial adhesion molecules. Phloretin is a plant-derived phytochemical that is mainly present in apples. Because phloretin is reported to promote antioxidative activities, we investigated the effects of phloretin on cytokine-induced expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (E-selectin) in human umbilical vein endothelial cells (HUVECs). Phloretin prevented TNF-alpha-stimulated upregulation of VCAM-1, ICAM-1, and E-selectin expression in a concentration-dependent manner. To the same extent as for TNF-alpha, phloretin also inhibited IL-1beta-induced upregulation in expression of all 3 adhesion molecules. Inhibition of cytokine-induced adhesion molecule expression for VCAM-1, ICAM-1, and E-selectin was detected already at the level of mRNA. Preincubation with phloretin dose-dependently attenuated TNF-alpha-stimulated adhesion of monocytic THP-1 cells to HUVECs and human aortic endothelial cells. Phloretin did not affect TNF-alpha-stimulated activation of nuclear factor kappaB (NF-kappaB) but inhibited activation of interferon regulatory factor 1, a transcription factor involved in the regulation of endothelial cell adhesion molecule expression. In human platelets, phloretin diminished adenosine diphosphate (ADP) and thrombin receptor-activating peptide-stimulated expression of the activated form of the GPIIb/IIIa complex and reduced platelet aggregation stimulated by ADP. Thus phloretin may have beneficial effects in the onset and progression of cardiovascular diseases.
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PMID:The flavonoid phloretin suppresses stimulated expression of endothelial adhesion molecules and reduces activation of human platelets. 1567 Dec 9

Ischemic heart diseases continue to be leading causes of death throughout the world. Blood platelets play a pivotal role not only in haemostasis but also in the pathogenesis of thrombosis and atherosclerosis, platelet aggregation being an essential step in the formation of either an effective haemostatic plug or an intravascular thrombus. The benefits of various antiplatelet therapies ranging from aspirin, ticlopidine, Clopidogrel, and intravenous platelet GPIIb/IIIa antagonists in various thromboembolic disorders are well documented. The studies of CAPRIE, CURE, PCI-CURE and MATCH have shown that the clopidogrel has a highly advantageous preventive effect in the ischaemic vascular diseases, that is why clopidogrel be highly recommended in the stroke prevention.
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PMID:[Clopidogrel in the prevention of stroke]. 1571 89

Inflammation is an important contributor to atherothrombosis. The C-reactive protein (CRP) is not only an excellent biomarker of inflammation, but it is also a direct participant in atherogenesis. CRP consistently predicts new coronary events, including myocardial infarction and death, in patients with ischemic heart disease. The predictive value of CRP is, in the majority of the studies, independent of and additive to that of the troponins and its levels can be modulated by statins. Prospective observational studies show that moderately elevated levels of CRP are associated with an adverse cardiovascular prognosis among healthy individuals. The availability of high sensibility assays for CRP should provide a valuable tool for identifying patients at risk of cardiovascular events in primary prevention in conjunction with lowering LDL cholesterol and may also have utility in the treatment of acute coronary syndromes with percutaneous coronary intervention (PCI) therapy. High CRP levels, associated with a higher risk, should suggest a more aggressive medical therapy in the long term and also an aggressive and invasive therapy in the short term, including the use of GP IIb/IIIa inhibitors, high doses of statins, and when a PCI is necessary, provisional stenting. Finally, CRP will provide a readily accessible marker for further testing of the inflammatory hypothesis in atherosclerosis.
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PMID:How to use the C-reactive protein in cardiac disease? 1578 80

Blood platelets play a crucial role in physiological haemostasis and in pathology of prothrombotic states, including atherosclerosis. In this paper, we review major factors underlying altered platelet reactivity, with special attention paid to abnormalities in platelet function in people with diabetes mellitus (DM). The overall picture of platelet abnormalities in DM, including altered adhesion and aggregation, is hypersensitivity of diabetic platelets to agonists. "Primed" diabetic platelets respond more frequently even to subthreshold stimuli, sooner become exhausted, consumed and finally hyposensitive, thus contributing to accelerated thrombopoiesis and release of 'fresh' hyperreactive platelets. In diabetes disturbed carbohydrate and lipid metabolism may lead to physicochemical changes in cell membrane dynamics, and consequently result in altered exposure of surface membrane receptors. These phenomena, together with increased fibrinogen binding, prostanoid metabolism, phosphoinositide turnover and calcium mobilisation often present in diabetic patients, contribute to enhanced risk of small vessel occlusions and accelerated development of atherothrombotic disease of coronary, cerebral and other vessels in diabetes. As platelet hypersensitivity in DM makes a major contribution to enhanced risk of thromboembolic macroangiopathy, and consequently enhanced morbidity and mortality, it validates use of antiplatelet agents in diabetic individuals. Platelet hyperreactivity may be cured with various antiplatelet drugs to a considerably large extent notwithstanding, evidence gathered from clinical and experimental surveys shows that this approach may not always be equally efficient in people with diabetes. Observations from clinical studies rather support the use of multifactorial strategy under such circumstances, like a combined therapy of aspirin plus either purinoreceptor blocker or GPIIb-IIIa antagonist.
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PMID:Blood platelet reactivity and its pharmacological modulation in (people with) diabetes mellitus. 1602 67

Platelet adhesion, activation, and aggregation at sites of vascular endothelial disruption caused by atherosclerosis are key events in arterial thrombus formation. Platelet tethering and adhesion to the arterial wall, particularly under high shear forces, are achieved through multiple high-affinity interactions between platelet membrane receptors (integrins) and ligands within the exposed subendothelium, most notably collagen and von Willebrand factor (vWF). Platelet adhesion to collagen occurs both indirectly, via binding of the platelet glycoprotein (GP) Ib-V-IX receptor to circulating vWF, which binds to exposed collagen, and directly, via interaction with the platelet receptors GP VI and GP Ia/IIb. Platelet activation, initiated by exposed collagen and locally generated soluble platelet agonists (primarily thrombin, ADP, and thromboxane A2), provides the stimulus for the release of platelet-derived growth factors, adhesion molecules and coagulation factors, activation of adjacent platelets, and conformational changes in the platelet alpha(IIb)beta3 integrin (GP IIb/IIIa receptor). Platelet aggregation, mediated primarily by interaction between the activated platelet GP IIb/IIIa receptor and its ligands, fibrinogen and vWF, results in the formation of a platelet-rich thrombus. Currently available antiplatelet drugs (aspirin [acetylsalicylic acid], dipyridamole, clopidogrel, ticlopidine, abciximab, eptifibatide, tirofiban) act on specific targets to inhibit platelet activation and aggregation. Elucidation of the multiple mechanisms involved in platelet thrombus formation provides opportunities for selectively inhibiting the pathways most relevant to the pathophysiology of atherothrombosis.
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PMID:The role of the platelet in the pathogenesis of atherothrombosis. 1625 28

Cell adhesion and proteolytic matrix degradation are central processes in atherosclerosis. Being a member of the family of ADAMs ("a disintegrin and metalloproteinase"), metargidin (ADAM15) combines a metalloproteinase domain and an RGD aminoacid sequence. We studied the potential role of ADAM15 as an adhesion receptor on endothelial cells and interactions between platelets and ADAM15 with respect to platelet adhesion, activation and thrombus formation. ADAM15 was found to be expressed on cultured endothelial cells (HUVEC). Platelet adhesion to immobilized recombinant ADAM15 was effectively enhanced under both static and high shear rate conditions reaching the maximum level of adhesion to fibrinogen. Consistently, platelet adhesion onto ADAM15 overexpressing endothelial cells was significantly increased. Adhesion to ADAM15 was reduced by blockade of GPIIb-IIIa using neutralizing anti-alpha(IIb)beta3 mAbs (7E3, 2G12), but not by anti-alpha(v)beta3 (LM609). Soluble ADAM15 binds to activated but not to resting GPIIb-IIIa. Moreover, platelets adherent to ADAM15 additionally attracted platelets under high shear rates indicating an initial role of platelet-ADAM15 interactions for thrombus formation. Furthermore, incubation of platelets with soluble ADAM15 showed a dose-dependent increase in secretion of CD62P and CD40L. ADAM15 is expressed on endothelial cells and can serve as an adhesion receptor for platelets via GPIIb-IIIa binding. Platelet adhesion to ADAM15 leads to platelet activation, secretion and promotes thrombus formation. Thus, ADAM15 may represent a novel target for antithrombotic strategies in cardiovascular pathologies.
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PMID:ADAM 15 is an adhesion receptor for platelet GPIIb-IIIa and induces platelet activation. 1626 72

Acute myocardial infarction in pregnancy is a rare condition. Two cases of suspected acute myocardial infarction during pregnancy are presented. Acute myocardial infarction in pregnancy is most often caused by atherosclerosis. Other possible aetiologies are dissection, embolism and arterial spasm. Acute coronary angiography is recommended as an early diagnostic procedure that does not present any risk to the embryo. Treatment with aspirin and heparin is safe, but there have been only a few case studies of the use of the newer antithrombotic drugs, chlopidogrel and GPIIb-IIIa inhibitors, in pregnant women.
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PMID:[Acute myocardial infarction during pregnancy]. 1722 65

Platelet microparticles (PMP) are released from activated platelets and play an important role in hemostasis, thrombosis and inflammation. Since platelets were recently found to demonstrate an intrinsic capacity for activating both classical and alternative pathways of the complement system, the present study extended these observations to PMP. PMP were generated by treating platelets with 10 microM A23187 (37 degrees C, 5 min). PMP were identified by flow cytometry, based on size, Annexin V binding, and expression of P-selectin and GPIIb (CD41). PMP expressed gC1qR/p33, a multifunctional cellular protein that was recently described to activate the classical complement cascade. PMP also expressed the classical pathway and contact system regulator, C1 inhibitor (C1-INH), as well as CD55 and CD59. Despite C1-INH expression, PMP supported classical pathway C4 activation in the presence of purified C1 and C4. Moreover, statistically significant deposition of C3b and C5b-9 was detected on PMP exposed to plasma, concurrently with expression of CD55 and CD59. These data provide the first evidence for the ability of PMP to support in situ complement activation. Complement activation contributes to a variety of vascular and inflammatory disease states including atherosclerosis and ischemia/reperfusion injury.
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PMID:Expression of complement components and inhibitors on platelet microparticles. 1843 23

Both the complement system and platelet-leukocyte aggregates are involved in chronic and acute stages of atherosclerosis. Properdin, a positive regulator of the complement system, is secreted by leukocytes and endothelial cells. In the present study, the role of properdin in the formation of platelet-leukocyte aggregates was investigated. Incubation of human whole blood with properdin (25-200 microg/ml) resulted in a dose-dependent formation of platelet-leukocyte aggregates, with an increase of up to 2.2-fold compared to controls (p < 0.05), as analysed by flow cytometry. In addition, properdin significantly amplified ADP-induced aggregation of platelets with leukocytes by 53% (p < 0.05), while it had no effect on ADP-induced aggregation of platelets alone. Consistent with these results, properdin did not activate platelets as shown by the expression of activated GPIIb/IIIa (PAC-1 epitope) and P-selectin (CD62P) on the platelet surface. However, properdin significantly induced expression of CD11b (MAC-1) on leukocytes by 12-fold (p < 0.05) as a measure of leukocyte activation. In conclusion, the complement system component properdin induces the formation of platelet-leukocyte aggregates via leukocyte activation. The data establish a link between the complement system and platelet-leukocyte aggregates with potential significance in atherosclerotic vascular disease.
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PMID:The complement factor properdin induces formation of platelet-leukocyte aggregates via leukocyte activation. 1879 42

Heart failure (HF) is more prevalent and evolves more rapidly in patients with renal failure (RF). Renal failure not only produces myocardial damage, but also induces the development of clinical heart failure thus making the treatment of these patients more difficult. The incidence of HF in patients with RF is around 15%. Renal function in patients with RF is lower than in the general population. This is true for patients with preserved and depressed left ventricular ejection fraction (LVEF). HF mortality increases 30% for every 1-mg/dL increase in creatinine and renal function should always be considered when assessing the cardiovascular risk and therapeutic alternatives of cardiovascular patients. Angiotensin converting enzyme inhibitors, Angiotensin receptor blockers and aldosterone blockers may cause acute renal failure and serum creatinine and potassium should be closely monitored. Chronic RF is a human model of accelerated atherosclerosis. It induces a rapid progression of coronary atherosclerosis and make atherosclerotic plaques more vulnerable to acute coronary syndromes (ACS) because of coagulation changes inherent to RF. Ischemia is also more frequent due to the imbalance between oxygen requirements and supplies. Chronic RF is associated with a worse outcome in patients with ACS and increases the risk of bleeding, and is associated with a higher mortality in patients under surgical or percutaneous coronary revascularization. Of the patients treated with an interventional coronary procedure (ICP), 3,3% suffer acute RF. Saline administration at a dose of 1 ml/kg/h for 12 hours before and 12 hours after ICP prevents the development of acute RF. Although the role of N-acetylcysteine is under discussion, taking into account the favourable risk profile of this drug, it seems reasonable to administer N-acetylcysteine in addition to saline administration. In ACS patients with severe RF, the risk of severe bleeding depends upon the anticoagulation regimen, increasing particularly when unfractionated heparin is used in combination with GP IIb/IIIa inhibitors.
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PMID:[Kidney disease: therapeutic implications in heart failure and coronary heart disease]. 1946 Apr 81


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