K Schror

..The rapid desensitization of the human prostacyclin (IP) in response to agonist binding has been shown in cell culture. Phosphorylation of the IP receptor by protein kinase C (PKC) has been suggested to be involved in this process...

..The inherent problems with all GP IIb/IIIa antagonists are the narrow therapeutic range because the same mechanisms are involved in hemostasis and thrombosis and their inability to inhibit platelet activation...

..At this time,there is no reason to change there commended daily maintenance dose of about 100 mg ASA without particular requirements in patients who need coronary protection...

..From a pharmacological point of view these compounds are likely to improve and enlarge the spectrum of available antiplatelet and antithrombotic drugs, respectively...

..In this context, it is interesting that CABG patients express transiently an immunoreactive COX-2 protein with lower molecular weight. Studies on the significance of this finding for ASA resistance are in progress...

..Despite of this optimistic outlook, the individual risk/benefit ratio of these new drugs, in particular in the area of anticoagulants, still needs to be defined...

..We summarize the mechanisms of actions of this class of agents, their cardiovascular risk as evident in multiple trials, the basis of their adverse risk profile, and our views on this issue...

..This might result in some drug interaction, i.e. with erythromycin and omeprazole. The half-life is approximately 10 h, resulting in about 2-fold accumulation of the drug during repeated administration...

..There is neither a generally accepted definition of insufficient responsiveness (against inhibitors of platelet function) nor any generally accepted procedure to measure it, including definition of normal range...

..Thus, regulation of gene transcription by PGE1 may contribute to tissue protection in critical ischemia of the lower limbs...

..However, the TARGET trial (tirofiban vs. abciximab in patients with acute coronary syndromes) is underway and probably will answer this question...

..Clearly, no drug treatment is without side effects. Thus, a balanced view of whether treatment with a certain drug is justified in terms of the benefit/risk ratio is always necessary. Aspirin is no exception...

..These data suggest beneficial effects of NAF on platelet hyperreactivity in experimental hypercholesterolemia which may also be relevant for its clinical use...

..The full text of this article is available online at http://circres.ahajournals.org...

..The present study specifically addresses the pharmacological interactions between selective COX-2 inhibitors and ASA and the possible consequences for the thrombotic risk during long-term treatment...

..Therefore, upregulation of HAS2 expression via EP(2) and IP receptors might contribute to the accumulation of HA during human atherosclerosis, thereby mediating proatherosclerotic functions of COX2...

..Therefore, PETN reduced infarct size and improved myocardial function after LAD occlusion and reperfusion. It is concluded that the intravenous administration of PETN might be of advantage in the treatment of acute myocardial ischemia...

..Platelets release the immune-modulating lipid sphingosine-1-phosphate (S1P). However, the mechanisms of platelet S1P secretion are not fully understood...

..These data demonstrate significant endothelium-protective actions of long-term oral naftidrofuryl in cholesterol-fed rabbits that involve inhibition of cholesterol-induced neutrophil activation...

..g. patients with advanced atherosclerotic disease) COX-2 inhibitors may result in platelet activation by inhibiting endothelial prostacyclin formation...

..The aim of this study was to evaluate the in vitro effects of MPA and FK upon platelet activation in healthy subjects...

..Anti-inflammatory analgesics, including ibuprofen and naproxen, are known to interfere with the antiplatelet effect of aspirin, presumably as a result of a drug-drug interaction at the level of platelet cyclooxygenase-1 (COX-1)...

..Taken together, it appears unlikely that calcification of atherosclerotic lesions contributes to thrombotic complications by an increased platelet adhesion...

..In contrast, clopidogrel treatment completely abolished ADP-induced expression of CD40L. Finally, the expression level of CD40L was shown to be upregulated by phorbol myristate acetate (PMA) in the promegakaryocytic cell line MEG-01...

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..In conclusion, vasodilatory prostaglandins might be considered as growth modulating endogenous mediators in vascular smooth muscle cells...

..Terbogrel appears to be a compound with an equipotent molar potency as thromboxane A2 synthase inhibitor and receptor antagonist...

..Whether these substances are superior to oral aspirin and/or clopidogrel in long-term prevention of acute arterial vessel occlusions remains to be determined...

..31 +/- 0.88 versus 9.15 +/- 0.88; means +/- SEM, n = 7, P < 0.05), whereas COX-1 levels did not change (13.45 +/- 1.11 versus 12.38 +/- 1.41; n = 7, P > 0.05)...

..It is not clear whether all of these patients with ischemic stroke respond normally to ASA or are hyporesponsive as assessed by inhibition of aggregation and thromboxane (TX) synthesis...

..This typology of aspirin resistance should help to clarify the mechanisms, the actual rate, and the possible clinical consequences of this phenomenon...

..This review discusses the regulation of HA-synthesis by prostaglandins and the evidence for a central role of cyclooxygenase-2/PGE2 in regulation of HA-synthesis during atherogenesis...

..The ability of human mononuclear cells to contribute to the NO production by expression of active inducible NO synthase (iNOS) is still discussed controversely...

..To validate the potential use as labels in 2-DE/MFA experiments, dyes were used for the differential analysis of the proteome of thrombin-stimulated human vascular smooth muscle cells (VSMCs)...

..This study focuses on the EP(3)-mediated hypertrophic action and investigates intracellular signalling pathways of the EP(3)-receptor subtype in the murine heart...

..This study examines the downstream mechanisms, particularly the role of nuclear factor of activated T-cells (NFAT)...

..This might be important for control of hSMC proliferation, migration and differentiation as well as inhibition of platelet aggregation...

..SELDI-TOF MS analysis of the pre-fractionation eluate confirmed a considerable reduction of sample complexity and an enhancement of selected protein signals...

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..The present study investigates possible effects of cholesterol enrichment and depletion, which have been shown to influence FGF-2-dependent signaling and SMC mitogenesis, on thrombin-induced FGF-2 release...

..We investigated the effect of high glucose on expression and function of vascular thrombin receptors...

..Therefore, ICAM-1 and VCAM-1 on smooth muscle cells may contribute to the inflammatory reaction in the vascular wall and may actively be involved in the progression and stability of atherosclerotic plaques...

..Vascular injury is also associated with enhanced formation of PGE2 and PGI2 (prostacyclin). This study investigates whether PGI2 and PGE2 modify the expression of PAR-1 and the cellular response to thrombin in human SMC...

..These results demonstrated that long-term desensitization and sequestration of hIP-R did not depend on structures located in the hIP-R C-terminus...

..This study is the first to describe increased transcriptional expression of a functionally active P2Y12 in response to thrombin in human vascular smooth muscle cells (SMC)...

..Cardioprotective actions of E-type prostaglandins may be mediated by this receptor subtype...

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..Whether this is associated with an increased risk of bleeding will be seen from the first phase III clinical trial in PCI-patients. The first results are expected at the end of the year...

..As expected, a marked pro-coagulant activity (FX activation, thrombin generation) was observed on the surface, in lysates, and on microparticles from HTF transfected cells. In contrast, no pro-coagulant activity of asHTF was observed...

..Thus, the present study does not provide evidence for an effect of HPA-1 polymorphism on the inter-individual variability in the platelet inhibitory effects of the three GPIIb/IIIa inhibitors approved for clinical use...

..The present study identified genes not hitherto recognized to be targets of PGI2 action, providing further insight into its cAMP-mediated effects on SMC growth, migration and matrix secretion...

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..It is concluded that paradoxical platelet activation by abciximab is a rare (<2%) phenomenon. HPA-1 b/b genotype might be a contributing factor but clearly does not predict platelet activation by GP IIb/IIIa inhibitors...

..ICAM-1 antibodies inhibited fibrinogen-induced Akt and p38 phosphorylation. Thus fibrinogen stimulates human SMC migration through binding to ICAM-1 and activation of Akt and p38...

..In conclusion, cerivastatin increased cytokine-induced iNOS and cyclooxygenase-2 expression, thus constituting NO-regulated growth inhibition of mesangial cells...

..Finally, sCD40L did not induce SMC migration. From these data it is concluded that CD40L activates mitogenic signalling and DNA synthesis but does not contribute to proliferation or migration of vascular SMC...

..Human cyclooxygenase-1bDeltaG was active but was not inhibited by acetaminophen. In conclusion, full length human cyclooxygenase-1b is clearly not the target of acetaminophen...

..It is concluded that ammonia triggers a prostanoid- and Ca(2+)-dependent glutamate exocytosis, which is essential for induction of ammonia-induced RNA oxidation...

..Thus, the expression of a COX-2a protein corresponding to the 67 kDa COX-2 protein is not clear. However, the marked shifting from COX-2 to COX-2a in platelets from some patients after CABG is a striking finding...

..Externalization of negatively charged phospholipids represents the most important mechanisms for whole cells. Additional yet unknown mechanisms appear to be involved in the procoagulant actions of MPs derived from apoptotic monocytes...

..The present data will now allow further studies on EP3 receptor-mediated signal transduction and its regulation...

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..Interestingly, 4N1-1 also stimulated activation-independent agglutination of different megakaryocytic and non-megakaryocytic cells. 4N1-1-induced cell agglutination but not platelet signaling was inhibited by anti-CD47 antibodies...

..Both might contribute to the mitogenic potency of FXa and FXa-stimulated matrix invasion of SMCs...

..It is concluded that vasoprotective actions of prostacyclin in vivo may in part be due to inhibition of expression of the growth regulatory gene Cyr61 at sites of vascular lesions...