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64 - Platelet–Endothelial Interactions
- from PART II - ENDOTHELIAL CELL AS INPUT-OUTPUT DEVICE
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- By Patricia B. Maguire, Conway Institute, University College Dublin, Ireland, Orina Belton, Conway Institute, University College Dublin, Ireland, Niaobh O'Donoghue, Conway Institute, University College Dublin, Ireland, Sandra Austin, Conway Institute, University College Dublin, Ireland, Judith Coppinger, Conway Institute, University College Dublin, Ireland
- Edited by William C. Aird, Harvard University, Massachusetts
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- Book:
- Endothelial Biomedicine
- Published online:
- 04 May 2010
- Print publication:
- 03 September 2007, pp 587-601
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- Chapter
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Summary
Platelets are anucleate, discoid cell fragments measuring 1.5 to 3.0 μM in diameter. They are derived from bone-marrow megakaryocytes that are normally maintained in a nonadhesive state, whereby they circulate freely in blood. Anucleate platelets are unique to mammals, with nonmammalian vertebrates (such as zebrafish) possessing nucleated thrombocytes. In 1865, a German anatomist Max Schultze (1825–1874) first described platelets as “spherules” much smaller than red blood cells. A few years later, in 1882, Giulio Bizzozero (1846–1901) found that platelets played a role in coagulation because they could clump and form a blood clot at the site of vessel wall injury. It was not until 1961, however, that the platelet aggregating effect of adenosine diphosphate was discovered (1) and, in the following year, that a machine for measuring aggregation (an aggregometer) was developed (2). The most important breakthroughs surrounded the discovery of proaggregatory platelet thromboxane A2 (TXA2) and antiaggregatory endothelial cell (EC) prostacyclin (PGI2), both discovered in the 1970s, along with the finding that aspirin inhibited prostaglandin synthesis and platelet activation. Indeed, finding inhibitors to platelets was exciting because it established the therapeutic possibility of preventing arterial thrombosis and ultimately vessel occlusion (the precipitating event in most myocardial infarctions and many strokes) by means of antiplatelet therapy.
The activation of platelets to arrest bleeding at sites of vascular damage results in platelet adhesion to the vessel wall, where they convert from passive, small discs into larger, flattened structures with extended pseudopods that act as a surface for the propagation of the clotting cascade. Activated platelets secrete and synthesize further platelet agonists, inflammatory mediators, and vasoactive substances.
Cyclooxygenase isoforms and atherosclerosis
- Orina Belton, Desmond J. Fitzgerald
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- Journal:
- Expert Reviews in Molecular Medicine / Volume 5 / Issue 9 / 7 March 2003
- Published online by Cambridge University Press:
- 13 February 2004, pp. 1-18
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- Article
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Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of arthritis and pain. However, their long-term use is limited by gastrointestinal (GI) side effects such as gastric ulcers. NSAIDs act by inhibiting an enzyme called cyclooxygenase. Cyclooxygenase (COX) catalyses the generation of prostaglandins from arachidonic acid. Two isoforms of the enzyme exist – COX-1 and COX-2 – both of which are targets for NSAIDs. Although they are associated with GI toxicity, NSAIDs have important antithrombotic and anti-inflammatory effects. The GI injury has been attributed to COX-1 inhibition and the anti-inflammatory effects to COX-2 inhibition. As COX-2 is traditionally viewed as an inducible enzyme, selective inhibition of COX-2 by ‘coxibs’ (selective COX-2 inhibitors) has been employed to achieve anti-inflammatory and analgesic effects without GI side effects. However, recently there have been suggestions that chronic administration of coxibs might increase the risk of cardiovascular events, such as atherosclerosis, compared with traditional NSAIDs. In vascular disease, there is increased expression of both COX-1 and COX-2, resulting in enhanced prostaglandin generation. The specific role of COX-1 and COX-2 in vascular regulation is still unknown but such knowledge is essential for the effective use of coxibs. Although more evidence is pointing to selective COX-1 inhibition as a therapeutic measure in inflammatory atherosclerosis, there are some studies that suggest that inhibition of COX-2 might have a potential benefit on atherosclerosis.