Increased Platelet Reactivity and Circulating Monocyte-Platelet Aggregates in Patients With Stable Coronary Artery Disease

Furman, Mark I.; Benoit, Stephen E.; Barnard, Marc R.; Valeri, C. R.; Borbone, Marie L; Becker, Richard C.; Hechtman, Herbert B.; Michelson, Alan D.

doi:10.1016/s0735-1097(97)00510-x

Cited by 463 publications

(197 citation statements)

References 48 publications

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“…Our previous studies (1,7,12), together with those of other investigators (2)(3)(4)(5)(6)(8)(9)(10)(11), highlighted the potential importance of platelet-monocyte complexes in inflammatory disease by demonstrating that activated platelets induce a proinflammatory phenotype characterized by the secretion of inflammatory mediators, including TNF-a, IL-8, and IL-1b (7)(8)(9)(10)(11). In this article, we report a specific mobilization of Ca 2+ and phosphorylation of Akt following coculture of monocytes with thrombin-activated platelets.…”

Section: Discussionmentioning

confidence: 57%

“…E levated numbers of circulating blood monocyte-platelet complexes were suggested to play a role in the pathogenesis of acute coronary syndromes and the earliest events of atherosclerosis (1)(2)(3). Increased monocyte-platelet complexes have also been observed in a number of diseases, including type 1 diabetes (4), rheumatoid arthritis (5), and end-stage renal disease (6), suggesting an important role in the pathogenesis of inflammatory diseases.…”

Section: The Uncoupling Of Monocyte-platelet Interactions From the Inmentioning

confidence: 99%

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The Uncoupling of Monocyte–Platelet Interactions from the Induction of Proinflammatory Signaling in Monocytes

Stephen

Emerson

Fox

et al. 2013

The Journal of Immunology

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Induction of an inflammatory monocyte phenotype by activated platelets is implicated in the pathogenesis of inflammatory diseases, including atherosclerosis. In this study, we investigated the early signaling events associated with this platelet-induced inflammatory phenotype. We report that coculture of human monocytes with activated platelets induces phosphorylation of Akt, together with rapid mobilization of intracellular Ca2+, and show that these signaling events can be uncoupled from monocyte binding to activated platelets. Specifically, Ab-inhibition studies and incubation of monocytes with activated platelet supernatant highlighted a role for secreted product(s) of activated platelets. We also identified a role for pertussis toxin–sensitive G protein–coupled receptors and excluded key candidates platelet-activating factor receptor and CCR5. Our results suggest that inhibition of monocyte–platelet interactions via PSGL-1 or P-selectin is not sufficient to prevent platelet-mediated monocyte activation in an inflammatory context. These findings have important implications for the development of therapeutics to treat diseases in which platelet–monocyte complexes are implicated in pathogenesis.

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Section: Discussionmentioning

confidence: 57%

Section: The Uncoupling Of Monocyte-platelet Interactions From the Inmentioning

confidence: 99%

The Uncoupling of Monocyte–Platelet Interactions from the Induction of Proinflammatory Signaling in Monocytes

Stephen

Emerson

Fox

et al. 2013

The Journal of Immunology

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“…CD62p (P-selection) is a 140 kD glycoprotein that is present in the granules of platelets and translocates rapidly to the cell surface after platelet activation, and is generally considered to be the gold marker of platelet activation [10,11]. There is evidence that patients with various types of CHD, including stable [12] and unstable [13] angina and acute myocardial infarction [14] have increased CD62p levels. Among all types of CHD, symptomatic stable angina is a clinical expression of myocardial ischemia associated with fixed atherosclerotic coronary stenosis; however, patients with acute coronary syndrome (ACS) constitute the major proportion of persons who require admission to cardiac units for urgent care, including invasive treatment and aggregate anticoagulant and antiplaque drug therapy [15].…”

Section: Discussionmentioning

confidence: 99%

Correlation between platelet gelsolin levels and different types of coronary heart disease

et al. 2011

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“…The effect of rFVIIa on platelet-leucocyte aggregation (PLA) was assessed by an adapted flow cytometry method (Furman et al, 1998;Joseph et al, 2001). Briefly, diluted whole blood was incubated in the presence of rFVIIa, 2AE5 mmol/l CaCl 2 and 2AE5 mmol/l GPRP as before in a total volume of 200 ll but in the absence of antibodies.…”

Section: Methodsmentioning

confidence: 99%

Activation of platelets in whole blood by recombinant factor VIIa by a thrombin‐dependent mechanism

et al. 2003

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Summary. Using a diluted whole blood method of flow cytometric analysis, we have shown that platelets could be activated in vitro in the presence of high concentrations (100 nmol/l) of recombinant factor (F) VIIa (rFVIIa; NovoSeven Ò ) and 2AE5 mmol/l calcium chloride. This was demonstrated by a significant increase in the mean percentage of platelets expressing CD62P and their mean fluorescent intensity (MFI) after 30 min versus platelets incubated with calcium or rFVIIa alone or diluted blood alone. The presence of rFVIIa and calcium increased the exposure of the PAC-1 activation epitope of glycoprotein (Gp) IIb/IIIa. This effect was equally influenced by the presence of calcium alone but not by rFVIIa. The effect of rFVIIa was time and concentration dependent. Thrombin generation was also necessary, as the effect of rFVIIa was completely abrogated by the additional presence of hirudin. Furthermore, soy bean trypsin inhibitor (SBTI) but not corn trypsin inhibitor (CTI) abrogated CD62P exposure, suggesting that thrombin was derived via FX but not FXII activation. Exposure of CD62P demonstrated a significant lag phase, sometimes of the order of > 30 min, as well as large intersubject variation. Significant platelet activation was observed at a concentration as low as 25 nmol/l rFVIIa. Platelet-leucocyte aggregation was also increased in the presence of 25 nmol/l rFVIIa and calcium. No significant difference was observed between levels of CD62P in diluted whole blood and platelet-rich plasma adjusted to an identical platelet count after their exposure to rFVIIa and calcium for 30 min.

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Increased Platelet Reactivity and Circulating Monocyte-Platelet Aggregates in Patients With Stable Coronary Artery Disease

Abstract: Patients with stable CAD have circulating activated platelets, circulating monocyte-platelet aggregates, increased platelet reactivity and an increased propensity to form monocyte-platelet aggregates.

Cited by 463 publications

References 48 publications

The Uncoupling of Monocyte–Platelet Interactions from the Induction of Proinflammatory Signaling in Monocytes

The Uncoupling of Monocyte–Platelet Interactions from the Induction of Proinflammatory Signaling in Monocytes

Correlation between platelet gelsolin levels and different types of coronary heart disease

Activation of platelets in whole blood by recombinant factor VIIa by a thrombin‐dependent mechanism

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