Plateletlipid interaction results in hyperreactivity of platelets and enhanced platelet adhesion to the endothelial monolayer i. Indeed, platelet activation and adhesion are critically important for the formation of intravascular thrombus leading to the occlusion of arterial supply and or venous drainage, resulting in. However, as the central role of platelets implicated in the etiology of arterial thrombotic diseases such as myocardial infarction and stroke became widely known, platelet function tests are now being promoted to monitor the efficacy of antiplatelet drugs and also. Platelet activation and blood coagulation are complementary, mutually dependent processes in haemostasis and thrombosis. Platelets play a critical role in atherothrombosis, in that they mediate thrombosis, the major pathogenic event in disease progression. A novel biomarker related to platelet activation and. Upon activation the discoid shape changes into a spherical form. Apr 18, 2018 platelet activation as measured by average cd62p expression increases with platelet storage. Acute and persistent platelet and coagulant activities in. During the course of atherogenesis, platelets interact with plasma lipids and engulf substantial amounts of proatherogenic lipids. The unique function of vwf in platelet adhesion and aggregation in highflow conditions is discussed below. However, the underlying mechanisms of ts iiamediated anti platelet activation effect are still poorly understood. Plateletlipid interaction results in hyperreactivity of platelets and enhanced platelet adhesion to. P2y 1 22 and p2y 12 23 adp and the thromboxane receptors tp.
Increased platelet activation in patients with stable and. Taken together, these findings suggest that platelet function may be modified as a consequence of copd. Blood coagulation, initiated by the coagulation cascades, is the second wave of thrombin generation and enhance phosphatidylserine exposure, can markedly potentiate cellbased thrombin generation and. The role of platelets in atherothrombosis article pdf available in hematology 20111. A key event in all these processes is platelet activation by matrix proteins notably collagen and by inducers at the arterial damage site. The preanalytical conditions are extremely important in the analysis of platelet activation markers. Platelet biology and implications for antiplatelet therapy in. Plateletinduced atherogenesis and atherothrombosis. Platelet production, structure and life span the normal platelet count is in the range 150. Platelet activation in vascular disease from animal studies to clinical consequences. Platelet activation and atherothrombosis the best evidence for the role of platelets in the pathogenesis of atherothrombosis is the numerous studies demonstrating platelet activation in acute vascular disease and the efficacy of antiplatelet therapies in the treatment of vascular disease.
Platelet activation and atherothrombosis researchgate. Upon activation, platelet surface pselectin is overexpressed, and platelets secret their granule contents into circulation. Platelet activation pathways and targets of current and novel antiplatelet drugs. The role of platelets in atherothrombosis sciencedirect. Pdf platelet activation and atherothrombosis david couoh. The process by which a resting platelet changes shape and becomes an integral part of clot. We investigated in vivo thromboxane tx and prostacyclin pgi2 biosynthesis and their determinants, as well as aspirin responsiveness, in young adult subjects with type 1 diabetes mellitus t1dm without overt cardiovascular disease and stable glycemic control. Platelets are anucleated blood cells that originate from the cytoplasm of megakaryocytes in the bone marrow and circulate to survey the integrity of the vascular system, where they discriminate. Platelets in atherothrombosis mayo clinic proceedings. Intracoronary atherothrombosis is the most common cause of the development of acute coronary syndrome acs, and plays a. Beside the lipidlowering effect, statins slow the progression of atherosclerosis by exerting antiinflammatory and platelet inhibiting effects.
Vasoconstrictive substances the greater the shear rate, the greater the role of vwf in platelet adhesion cytokines conformational change platelet activation fibrinogen extracellular matrix collagen vi collagen iiii collagen 1170 rev esp cardiol. Review articles and textbooks were used to inform our discussion of the physiology of platelets, and current understanding of the biochemical mechanisms involved in platelet activation. Coagulation, also known as clotting, is the process by which blood changes from a liquid to a gel, forming a blood clot. Pdf the role of platelets in atherothrombosis researchgate. Pdf platelet activation and atherothrombosis david.
However, the underlying mechanisms of ts iiamediated antiplatelet activation effect are still poorly understood. Tanshinone iia ts iia, a multipharmaceutical compound from traditional chinese herb, is effective for treatment of atherothrombosis. Overview of therapeutic approaches for cholesterol. Scramblase activation results in the loss of phospholipid asymmetry and ps exposure on the outer leaflet of the. Dec 10, 2011 these endogenous agonists can act in an autocrine or paracrine manner to enhance platelet activation by engaging specific g protein coupled receptors. Nov 27, 2009 platelet activation and atherothrombosis. B upon activation, platelets and neutrophils interact through adhesion molecules and soluble mediators and thereby reciprocally amplify activatory signals. Article information, pdf download for platelet biology and implications for antiplatelet.
These molecular pathways of amplification of platelet activation are the target of. Activated platelets come in a procoagulant state after a prolonged elevation in cytosolic. Read platelet thrombin receptor antagonism and atherothrombosis, european heart journal on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. It potentially results in hemostasis, the cessation of blood loss from a damaged vessel, followed by repair. Role of plateletderived microvesicles as crosstalk mediators. However, aspirin and p2y12 inhibitors target the thromboxane a2 and the adp p2y12 platelet activation pathways and minimally affect other pathways, while agonists such as thrombin, considered to be the most potent platelet activator, continue to stimulate platelet activation and thrombosis. Platelet thrombin receptor antagonism and atherothrombosis. After platelet activation by potent agonists, high levels of sustained intracellular calcium triggers scramblase activity. Platelet activation is crucial for wound healing at sites of endothelial cell. Lipoproteins, platelets, and atherothrombosis sciencedirect. Thrombin not only converts fibrinogen to fibrin but also serves as a potent platelet agonist, thereby augmenting platelet activation and aggregation.
Platelet activation, which is known to be associated with cardiovascular risk factors that accelerate atherogenesis 3, can easily be estimated by. Lipoproteins, platelets and atherothrombosis request pdf. Aspirin resistance is the inability of aspirin to reduce platelet production of thromboxane a2 and thereby platelet activation and aggregation. The p2y 12 receptor is the major receptor able to amplify and sustain platelet activation in response to adp. The discussion conveys the importance of platelet activation in acute coronary ischemia, as well as in other vascular conditions, such as ischemic stroke. The role of antiplatelet therapy such as aspirin in reducing the risk of many cardiovascular and cerebrovascular disorders is also well established9. Less is known of the persistent effects of a thrombus on. Platelets are central mediators of thrombosis and hemostasis. Increased levels of activated platelets or serological markers of platelet activation have been reported in patients with vascular disease 4449. Coagulation factors, phosphatidylserine, platelet receptors, thrombin summary platelet activation and blood coagulation are complementary, mutually dependent processes in haemostasis and thrombosis. Moreover, platelet activation is further increased in patients with copd during an acute exacerbation.
We suggest that platelet activation represents a novel mechanism linking copd, inflammation and cardiovascular disease. Microparticle content measured with thrombolux varies greatly with age see figure. Platelets, atherothrombosis, and atherosclerosis peerj. Plateletderived microvesicles represent about 7090% of all circulating mv pool and contribute to many biological processes berckmans et al. Aspirin resistance can be detected by laboratory tests of platelet thromboxane a2 production or platelet function that depend on. Activation of platelets in the blood flow is provoked by exposure. Jennings, journalthrombosis and haemostasis, year2009.
Preincubation with rbc facilitates platelet activation or recruitment, and this facilitatory effect is completely suppressed by the administration of a single, high dose of aspirin 500 mg, whereas a lower dosage 50 mgd for up to 15 days, a regimen that would completely inactivate platelet cox1, is ineffective. Pdf mechanisms of platelet activation, adhesion and. Jun 19, 2015 persistent platelet activities in atherothrombosis. They are critical for the pathogenesis of human carotid atherosclerosis, thromboembolism, and thrombotic stroke. Increasing degrees of aspirin resistance may correlate independently with increasing risk of cardiovascular events. Need for new strategies to protect against plateletmediated atherothrombosis. Plateletderived microvesicle release and clearance. The major goal of traditional platelet function tests has been to screen and diagnose patients who present with bleeding problems. Several markers of platelet activation such as pselectin, cd40l, pf4, and gp iibiiia have been identified to correlate with the presence of inflammation and atherosclerosis 1719, 26. Platelets in inflammation and atherogenesis journal of clinical. Prevention of atherothrombosis by platelet inhibiting drugs. Platelet activation and aggregation are ultimately responsible for the progression and clinical presentations of atherothrombotic disease.
Platelets and their activation have a pivotal role in the development of atherosclerotic diseases such as acute myocardial infarction ami, stroke and peripheral arterial occlusion. Aug 31, 2016 plateletderived microvesicle release and clearance. Antiplatelet agents for the treatment and prevention of atherothrombosis. The role of the platelet in the pathogenesis of atherothrombosis. We investigated whether platelet inhibition by simvastatin correlates with the statin effects on lipid lowering, inflammation, oxidative stress, and endothelial and platelet activation. Blood platelets play a major role in atherosclerosis and thrombosis 1. Thrombin not only converts fibrinogen to fibrin but also serves as a potent platelet agonist, thereby augmenting platelet activation and. Platelets in atherothrombosis diagnostic and prognostic. The current standard of care, dual oral antiplatelet.
Antiplatelet agents for the treatment and prevention of coronary atherothrombosis. Request pdf role of platelets in atherothrombosis platelets play a pivotal role in atherothrombosis and therefore are primary targets of antithrombotic therapy. Thus, platelet activation is amplified by several secondary feedback pathways. At the site of vascular injury, platelet accumulation i. This results in platelet activation and transformation of the integ rin receptors.
Role of plateletderived microvesicles as crosstalk. The atherothrombotic process relies on collagen and adpreceptorinduced platelet activation as well as on thrombinfibrin generation via the extrinsic and intrinsic coagulation pathways. Acute and persistent platelet and coagulant activities in atherothrombosis. For full access to this pdf, sign in to an existing account, or purchase an annual subscription. Platelets interact with several coagulation factors, while the coagulation product thrombin is a potent platelet activating agonist. Initial platelet activation occurs via binding of several agonists, like thrombin, adp and collagen not shown in this picture to their receptor on the platelet surface. Platelets interact with several coagulation factors, while the coagulation product thrombin is a potent plateletactivating agonist.
Rabbits are valuable for studying human atherothrombosis, because they have mechanisms of lipoprotein metabolism and platelet activation that are more similar to those of humans than smaller rodents such as rats and mice. Platelet activation, initiated by exposed collagen and locally generated soluble platelet agonists primarily thrombin, adp, and thromboxane a 2, provides the stimulus for the release of plateletderived growth factors, adhesion molecules and coagulation factors, activation of adjacent platelets, and conformational changes in the platelet. The illustration depicts adhesion molecules and neutrophilderived mediators that play a role in platelet activation and atherothrombosis and constitute potential therapeutic targets gray. Aug 20, 2012 platelet activation, initiated by exposed collagen and locally generated soluble platelet agonists primarily thrombin, adp, and thromboxane a 2, provides the stimulus for the release of plateletderived growth factors, adhesion molecules and coagulation factors, activation of adjacent platelets, and conformational changes in the platelet. Coincidentally, exposed tissue factor initiates thrombin generation. Platelet activation is persistently enhanced, and its inhibition by lowdose aspirin is impaired in type 2 diabetes mellitus. Tanshinone iia prevents platelet activation and down.
Pdf platelets have evolved highly specialized adhesion. Clinical manifestations of atherothrombotic disease, such as acute coronary syndromes, cerebrovascular events, and peripheral arterial disease, are major causes of mortality and morbidity worldwide. As shown in our previous study, plateletderived microvesicles pmvs generated in response to oxidant insult could activate cd36mitogen. As shown in our previous study, platelet derived microvesicles pmvs generated in response to oxidant insult could activate cd36mitogen. The preanalytical conditions are extremely important. Indeed, platelet activation and adhesion are critically important for the formation of intravascular thrombus leading to the occlusion of arterial supply andor venous drainage, resulting in. Role of antiplatelet therapies in preventing atherothrombosis. Atherosclerosis and atherothrombosis have aptly been described as an insidious cycle of acute inflammation and thrombosis, often remaining clinically silent until the development of a catastrophic cardiovascular event 1. The mechanism of coagulation involves activation, adhesion and aggregation of platelets, as well as deposition and maturation of fibrin. Cyclooxygenase2 expression and inhibition in atherothrombosis. Consistent with a plateletactivating role for type i and iii collagens in atherothrombosis is the observation that, in serial cross sections of human atherosclerotic plaques, the areas of high platelet deposition are enriched in. Basic principles of platelet biology and clinical implications jstage.
However, platelet age is a poor predictor of platelet activation status due to the high variability of donors and the effects of processing factors listed above. Overview of therapeutic approaches for cholesterol lowering. Lipoproteins, platelets, and atherothrombosis composition and. Antiplatelet agents for the treatment and prevention of. At the same time, circulating thromboxane a 2 and adp, in concert with other soluble agonists eg. Adhesion of platelets is the primary step in the platelet haemostasis followed by platelet activation and platelet aggregation. The role of platelets in atherothrombosis hematology. Review articles and textbooks were used to inform our discussion of the physiology of platelets, and current understanding. Platelet activation leads to densegranule secretion of adp, which activates p2y 12, inducing amplification of aggregation, procoagulant, and proinflammatory responses adapted from storey, 2008. Platelet activation, atherothrombosis, antiplatelet therapy, ami, stroke, gpvi, prasugrel, ticagrelor, peripheral arterial occlusion, vwf. Txa 2 causes platelet activation and vasoconstriction, enhances chemoattractant mcp1 and adhesion molecule expression on endothelial cells, 4346 and increases leukocyte adhesiveness. Less is known of the persistent effects of a thrombus on atherosclerosis. Platelet activation mechanisms and role of the p2y 12 receptor.
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