Reduction of monocyte-platelet interaction and monocyte activation in patients receiving antiplatelet therapy after coronary stent implantation

May, Andreas E.; Neumann, Franz‐Josef; Gawaz, Meinrad; Ott, I.; Walter, Hanna; Schömig, Albert

doi:10.1093/oxfordjournals.eurheartj.a015200

Cited by 47 publications

(41 citation statements)

References 39 publications

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“…In the presence of either SC560-treated (but not aspirin) or COX-1 Ϫ/Ϫ platelets, hypercholesterolemia-induced leukocyte adhesion was reduced, especially by platelet-bearing leukocytes, suggesting that platelet-derived COX-1 products promote these hypercholesterolemia-induced blood cell interactions, possibly through transcellular production of mediators or activation of signaling pathways that induce adhesion molecule expression and/or render platelet-bearing leukocytes more responsive to activation signals (14,29). Our inability to demonstrate an influence of aspirin-treated platelets on platelet-leukocyte and leukocyte-vessel wall adhesion in HC venules is consistent with aspirin's reported failure to inhibit increased expression of P-selectin on platelets and plateletleukocyte aggregation associated with several CVD, such as ischemic heart disease (31), intracoronary stenting (21), and atherosclerosis (15).…”

Section: Discussionsupporting

confidence: 81%

Roles of platelet and endothelial cell COX-1 in hypercholesterolemia-induced microvascular dysfunction

Tailor

Wood²,

Wallace³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Aspirin is a common preventative therapy in patients at risk for cardiovascular diseases, yet little is known about how aspirin protects the vasculature in hypercholesterolemia. The present study determines whether aspirin, nitric oxide-releasing aspirin (NCX-4016), a selective cyclooxygenase (COX)-1 inhibitor (SC560), or genetic deficiency of COX-1 prevents the inflammatory and prothrombogenic phenotype assumed by hypercholesterolemic (HC) venules. Aspirin or NCX-4016 (60 mg/kg) was administered orally for the last week of a 2-wk HC diet. COX-1-deficient (COX-1 Ϫ/Ϫ ) and wild-type (WT) mice were transplanted with WT (WT/COX-1 Ϫ/Ϫ ) or COX-1 Ϫ/Ϫ (COX-1 Ϫ/Ϫ /WT) bone marrow, respectively. HC-induced adhesion of platelets and leukocytes in murine intestinal venules, observed with intravital fluorescence microscopy, was greatly attenuated in aspirin-treated mice. Adhesion of aspirin-treated platelets in HC venules was comparable to untreated platelets, whereas adhesion of SC560-treated platelets was significantly attenuated. HC-induced leukocyte and platelet adhesion in COX-1 Ϫ/Ϫ /WT chimeras was comparable to that in SC560-treated mice, whereas the largest reductions in blood cell adhesion were in WT/COX-1 Ϫ/Ϫ chimeras. NCX-4016 treatment of platelet recipients or donors attenuated leukocyte and platelet adhesion independent of platelet COX-1 inhibition. Platelet-and endothelial cell-associated COX-1 promote microvascular inflammation and thrombogenesis during hypercholesterolemia, yet nitric oxide-releasing aspirin directly inhibits platelets independent of COX-1. aspirin; NCX-4016; platelets; leukocytes; cyclooxygenase ASPIRIN THERAPY IS WIDELY used in patients at risk of developing atherosclerosis and thrombosis. The therapeutic efficacy of aspirin in cardiovascular diseases (CVD) is attributed to its platelet-inhibitory function, which results from irreversible inhibition of cyclooxygenase (COX) activity and thromboxane (Tx) generation (2, 33). Although platelets are a rich source of the constitutive isoform of COX (COX-1), endothelial cells also express COX-1 in addition to the inducible isoform, COX-2. This likely accounts for evidence implicating endothelial cell COX-1 inhibition in the beneficial effects of aspirin (but not COX-2 inhibitors) on the inflammation associated with atherosclerotic lesions in apolipoprotein E-deficient and lowdensity lipoprotein receptor-deficient mice (8,25). While the anti-inflammatory action of aspirin in this setting may also result from platelet inhibition (8), nonsteroidal anti-inflammatory drugs (NSAIDs) and their metabolites (i.e., salicylate) can directly interfere with adhesion of inflammatory cells to vascular endothelium, both in vitro (5, 11) and in vivo (1, 6). Hypercholesterolemia, diabetes, hypertension, and other risk factors for CVD promote inflammatory and thrombogenic responses in lesion-prone arteries. Similar responses are detected in microvasculature before the development of atherosclerotic lesions and may render tissues even more vulnerable to ischemic t...

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Section: Discussionsupporting

confidence: 81%

Roles of platelet and endothelial cell COX-1 in hypercholesterolemia-induced microvascular dysfunction

Tailor

Wood²,

Wallace³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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“…Reductions in MPAs have been demonstrated after administration of monoclonal antibodies against P-selectin glycoprotein ligand 1 and the blockade of P-selectin, 33 and although antiplatelet therapy seems to reduce MPAs, 34 anticoagulation has little effect. 35 At present, there are no convincing clinical trial data to suggest a beneficial role on mortality of either anticoagulation or …”

Section: Discussionmentioning

confidence: 99%

Increased Formation of Monocyte-Platelet Aggregates in Ischemic Heart Failure

Wrigley

Shantsila

Tapp

et al. 2013

Circ: Heart Failure

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Background— Cross-talk between monocytes and platelets is reflected by the formation of monocyte-platelet aggregates (MPAs). It is not known whether MPAs are affected in heart failure (HF), and we examined differences in patients with acute HF (AHF), stable HF (SHF), stable coronary artery disease (CAD) without HF, and healthy controls (HCs). Methods and Results— MPAs were analyzed by flow cytometry for the 3 monocyte subsets (CD14++CD16-CCR2+ [Mon1], CD14++CD16+CCR2+ [Mon2] and CD14+CD16++CCR2– [Mon3]) in patients with AHF (n=51), SHF (n=42), stable CAD (n=44), and HCs (n=40). Counts of total MPA and MPAs associated with Mon1 and Mon2 were significantly higher in AHF compared with SHF, CAD, and HCs ( P <0.001 for all). The proportion of Mon1 aggregated with platelets was increased in AHF compared with SHF ( P =0.033), CAD ( P <0.001), and HCs ( P <0.001). A higher percentage of Mon3 aggregated with platelets was also seen in AHF compared with SHF ( P =0.012) and HCs ( P <0.001) but not compared with CAD ( P =0.647). MPAs associated with Mon2 were significantly lower in patients who experienced adverse clinical outcomes of death or rehospitalization compared with those who remained free of events ( P =0.03). Mon2 count remained an independent negative predictor of combined death and rehospitalization after adjustment for age, left ventricular ejection fraction, creatinine, and brain natriuretic peptide (hazard ratio, 0.58 [95% CI, 0.34–0.98]; P =0.043). Conclusions— MPA formation in patients with both acute and stable HF is increased and seems to be confined to monocytes from Mon1 and Mon2 subsets. MPAs associated with Mon2 seem to be negatively predictive of a worse prognosis in AHF.

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“…In patients with acute MI, platelet-leukocyte interaction is increased compared with controls, and P-selectin levels have been shown to remain increased for at least a month following initial presentation in ACS patients with non-ST segment elevation [83], and even in patients with stable coronary artery disease. Antiplatelet therapy with a P2Y 12 antagonist plus aspirin was shown to decrease platelet-monocyte interactions that occur after coronary stenting [84], an effect not observed with anticoagulants plus aspirin, suggesting that P2Y 12 antagonism had an anti-inflammatory effect distinct from its antithrombotic mode of action. Targeting of CD40L, another platelet-derived inflammatory protein, either through a blocking antibody [85] or via gene-targeting [86], greatly inhibited lesion progression in either LDLR )/) or apoE )/) mice, respectively.…”

Section: Evolving Paradigm On the Relationship Of Thrombosis To Inflamentioning

confidence: 97%

Therapeutic approaches in arterial thrombosis

Phillips

Conley

Sinha

et al. 2005

Journal of Thrombosis and Haemostasis

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Summary. The current standard of care for the treatment of arterial thrombosis includes anticoagulants and three classes of antiplatelet agents -aspirin, thienopyridines and glycoprotein IIb-IIIa antagonists. Although these drugs have had a significant impact on morbidity and mortality in several patient populations, up to 15% of the high risk patients with acute coronary syndrome continue to suffer from ischemic events. This problem may occur, in part, because the platelets in many patients are non-responsive to aspirin and clopidogrel. Murine models now indicate that platelets are not only responsible for arterial occlusion, they are also involved in the progression of atherosclerotic disease. New opportunities have emerged identifying potential targets and strategies for drug discovery suited to address these deficiencies by more effectively modulating platelet adhesion, thrombus growth, thrombus stability and the pro-inflammatory activity of platelets. In addition, a growing need has emerged for the development of bedside devices capable of bringing personalized medicine to patients being treated with antithrombotic drugs in order to measure the pharmacodynamic activities of new therapies, to assess the activities achieved by combined antithrombotic therapy, and to identify patients that fail to respond.

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Reduction of monocyte-platelet interaction and monocyte activation in patients receiving antiplatelet therapy after coronary stent implantation

Cited by 47 publications

References 39 publications

Roles of platelet and endothelial cell COX-1 in hypercholesterolemia-induced microvascular dysfunction

Roles of platelet and endothelial cell COX-1 in hypercholesterolemia-induced microvascular dysfunction

Increased Formation of Monocyte-Platelet Aggregates in Ischemic Heart Failure

Therapeutic approaches in arterial thrombosis

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