The effects of antiplatelet agents on platelet–leukocyte aggregations in patients with acute cerebral infarction

Cao, Yongjun; Yinming, Wang; Zhang, Jing; Zeng, Yanjun; Liu, Chunfeng

doi:10.1007/s11239-007-0190-x

Cited by 22 publications

(11 citation statements)

References 28 publications

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“…A number of therapeutic molecules have been used to investigate the inhibition of PMC, including clopidogrel (inhibition of ADP-mediated platelet activation) and Abciximab (GPI-IbIIIa antibody). Clopidogrel greatly reduces PMC in patients with atherosclerotic diseases and has been shown to reduce P-selectin expression and CD40L release [122][123][124]. Although some studies suggest otherwise by reporting an increase in the expression of RANTES upon clopidogrel administration [125], much evidence points to an efficient inhibition of PMC formation by clopidogrel.…”

Section: Intervention Possibilitiesmentioning

confidence: 76%

Molecular and functional interactions among monocytes, platelets, and endothelial cells and their relevance for cardiovascular diseases

Gils

Zwaginga

Hordijk

2008

Journal of Leukocyte Biology

258

211

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Platelets, monocytes, and endothelial cells are instrumental in the development and progression of cardiovascular diseases. Inflammation, a key process underlying cardiovascular disorders, is accompanied and amplified by activation of platelets and consequent binding of such platelets to the endothelium. There, platelet-derived chemokines, in conjunction with increased expression of adhesion molecules, promote the recruitment of circulating monocytes that will eventually migrate across the endothelial lining of the vessel into the tissues. Additionally, platelets may already become activated in the circulation and may form platelet-monocyte complexes, which show increased adhesive and migratory capacities themselves but also facilitate recruitment of noncomplexed leukocytes. They should therefore be considered as important mediators of inflammation. In molecular terms, these events are additionally governed by chemokines released and presented by the endothelium as well as the different classes of endothelial adhesion molecules that regulate the interactions among the various cell types. Most important in this respect are the selectins and their ligands, such as P-selectin glycoprotein (GP) ligand 1, and the integrins binding to Ig-like cell adhesion molecules as well as to GP, such as von Willebrand factor, present in the extracellular matrix or on activated endothelium. This review aims to provide an overview of these complex interactions and of their functional implications for inflammation and development of cardiovascular disease.

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Section: Intervention Possibilitiesmentioning

confidence: 76%

Molecular and functional interactions among monocytes, platelets, and endothelial cells and their relevance for cardiovascular diseases

Gils

Zwaginga

Hordijk

2008

Journal of Leukocyte Biology

258

211

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“…P value refers to comparison between responders and non-responders to dipyridamole on the PFA-100 pathways (McCabe et al, 2004b;Weyrich et al, 2005;Cao et al, 2009) and these data suggest that it may ultimately inhibit ADP-induced platelet reactivity, perhaps through intraplatelet inhibition of phosphodiesterase E5 and phosphodiesterase 3A, thereby increasing intraplatelet cGMP and cAMP (Kim & Liao, 2008). Alternatively, it may act indirectly by reducing adenosine uptake by erythrocytes or endothelial cells, thus increasing adenosine that is available to bind to platelet adenosine receptors, which could reduce the propensity for platelet degranulation (Haslam et al, 1999;Kim & Liao, 2008).…”

Section: Discussionmentioning

confidence: 99%

Enhanced ex vivo inhibition of platelet function following addition of dipyridamole to aspirin after transient ischaemic attack or ischaemic stroke: First results from the TRinity AntiPlatelet responsiveness (TrAP) study

Tobin¹,

Kinsella²,

Collins

et al. 2011

Br J Haematol

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SummaryEx vivo dipyridamole 'non-responsiveness' has not been extensively studied in ischaemic cerebrovascular disease. Platelet surface marker expression, leucocyte-platelet complex formation and inhibition of platelet function at high shear stress as detected by the PFA-100 Ò Collagen-Adenosinediphosphate (C-ADP) and Collagen-Epinephrine cartridges was assessed in 52 patients within 4 weeks of transient ischaemic attack (TIA) or ischaemic stroke on aspirin, and then 14 d (14 d) and >90 d (90 d) after adding dipyridamole. A novel definition of 'Dipyridamole non-responsiveness' was used. The median C-ADP closure time increased following addition of dipyridamole, remained elevated at 90 d (P £ 0AE03), and was unaffected by aspirin dose. 59% at 14 d and 56% at 90 d were 'dipyridamole nonresponders' on the PFA-100. The proportion of non-responders at 14 and 90 d was similar (P = 0AE9). Compared with baseline (4AE6%), median monocyte-platelet complexes increased at 14 d (5AE0%, P = 0AE03) and 90 d (4AE9%, P = 0AE04). Low C-ADP closure times were associated with increased monocyte-platelet complexes at 14 d (r = )0AE32, P = 0AE02) and 90 d (r = )0AE33, P = 0AE02). Monocyte-platelet complexes increased in the subgroup of dipyridamole non-responders on the PFA-100 (P £ 0AE045), but not in responders (P ‡ 0AE5), at 14 and 90 d versus baseline. Additional inhibition of platelet function has been detected with the PFA-100 when dipyridamole is added to aspirin. Elevated monocyte-platelet complexes may contribute to ex vivo dipyridamole non-responsiveness.

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“…These hetero-aggregates seem to play an important role in the pathophysiology of cardiovascular and cerebrovascular diseases, such as angina pectoris and stroke [13][14][15][16][17][18][19][20][21], as well as in the development of vascular complications of diabetes [22,23].…”

Section: Introductionmentioning

confidence: 99%

Roles of Mac-1 and glycoprotein IIb/IIIa integrins in leukocyte–platelet aggregate formation: Stabilization by Mac-1 and inhibition by GpIIb/IIIa blockers

Patkó

Császár²,

Acsády

et al. 2012

Platelets

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Circulating platelet-leukocyte hetero-aggregates play an important role in acute cardiovascular events and hypersensitivity reactions. The association involves the receptor families of selectins and integrin. The objective of this study was to investigate the role of CD11b/CD18 integrin (Mac-1) in hetero-aggregate formation and search for a counter-receptor on platelets ready to interact with Mac-1. As a model of leukocytes, Mac-1 presenting Chinese hamster ovary (CHO) cells were used to evaluate the role of Mac-1 in hetero-aggregate formation. The amount of CHO cell-bound active and inactive platelets was measured by flow cytometry, while the counter-receptors on platelets were identified via using blocking antibodies. We observed significant platelet adhesion on Mac-1-bearing cells when platelet-rich plasma or activated platelets were present. Inactive platelets did not adhere to Mac-1-bearing cells. Addition of fibrinogen, a ligand of Mac-1 significantly increased platelet binding. CD40L was demonstrated to act similarly on Mac-1. Inhibition of platelet GpIIb/IIIa completely abolished CHO cell-platelet aggregation. In our study, we have shown for the first time that Mac-1 mediates the formation of hetero-aggregates without selectin tethering when Mac-1 ligands such as fibrinogen or CD40L are present and blockers of platelet GpIIb/IIIa are able to diminish this interaction.

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The effects of antiplatelet agents on platelet–leukocyte aggregations in patients with acute cerebral infarction

Abstract: PMA are a sensitive biomarker to platelet activation in patients with cerebral infarction. In addition, although both aspirin and clopidogrel lowered the level of PMA, clopidogrel is a more effective treatment than aspirin in inhibiting platelet activation.

Cited by 22 publications

References 28 publications

Molecular and functional interactions among monocytes, platelets, and endothelial cells and their relevance for cardiovascular diseases

Molecular and functional interactions among monocytes, platelets, and endothelial cells and their relevance for cardiovascular diseases

Enhanced ex vivo inhibition of platelet function following addition of dipyridamole to aspirin after transient ischaemic attack or ischaemic stroke: First results from the TRinity AntiPlatelet responsiveness (TrAP) study

Roles of Mac-1 and glycoprotein IIb/IIIa integrins in leukocyte–platelet aggregate formation: Stabilization by Mac-1 and inhibition by GpIIb/IIIa blockers

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