Clopidogrel reduces platelet-leucocyte aggregation, monocyte activation and RANTES secretion in type 2 diabetes mellitus

Harding, Scott; Sarma, Jaydeep; Din, Jehangir; Maciocia, Paul; Newby, D E; Fox, Keith A.A.

doi:10.1136/hrt.2005.083006

Cited by 32 publications

(20 citation statements)

References 5 publications

(1 reference statement)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although we did not observe any direct vascular effects associated with the increase in plasma TNF-α concentrations, we did observe a 50% relative increase in PMA, a measure of platelet activation. We have previously observed an approximate 20% fall in PMA following treatment with clopidogrel,22 suggesting that the increase associated with treatment with etanercept is clinically relevant. These findings are consistent with previous in vitro studies showing that TNF-α can cause an increase in platelet aggregation in patients with heart failure, probably through activation of the arachadonic acid pathway 25 26.…”

Section: Discussionmentioning

confidence: 94%

See 1 more Smart Citation

Cardiovascular effects of tumour necrosis factor α antagonism in patients with acute myocardial infarction: a first in human study

Padfield

Din

Koushiappi

et al. 2013

Heart

View full text Add to dashboard Cite

ObjectiveThe inflammatory cytokine, tumour necrosis factor α (TNF-α), exerts deleterious cardiovascular effects. We wished to determine the effects of TNF-α antagonism on endothelial function and platelet activation in patients with acute myocardial infarction.Design and setting and patientsA double-blind, parallel group, randomised controlled trial performed in a tertiary referral cardiac centre. 26 patients presenting with acute myocardial infarction randomised to receive an intravenous infusion of etanercept (10 mg) or saline placebo.Main outcome measuresLeucocyte count, plasma cytokine concentrations, flow cytometric measures of platelet activation and peripheral vasomotor and fibrinolytic function were determined before and 24 h after study intervention.ResultsConsistent with effective conjugation of circulating TNF-α, plasma TNF-α concentrations increased in all patients following etanercept (254±15 vs 0.12±0.02 pg/ml; p<0.0001), but not saline infusion. Etanercept treatment reduced neutrophil (7.4±0.6 vs 8.8±0.6×109 cells/l; p=0.03) and plasma interleukin-6 concentrations (5.8±2.0 vs 10.6±4.0 pg/ml; p=0.012) at 24 h but increased platelet–monocyte aggregation (30±5 vs 20±3%; p=0.02). Vasodilatation in response to substance P, acetylcholine and sodium nitroprusside, and acute tissue plasminogen activator release were unaffected by either treatment (p>0.1 for all).ConclusionsFollowing acute myocardial infarction, etanercept reduces systemic inflammation but increases platelet activation without affecting peripheral vasomotor or fibrinolytic function. We conclude that TNF-α antagonism is unlikely to be a beneficial therapeutic strategy in patients with acute myocardial infarction.

show abstract

Section: Discussionmentioning

confidence: 94%

“…The primary outcome measure was PMA. On the basis of previous work examining the effect of clopidogrel on PMA22 we estimated that a 5% absolute change in PMA would be of clinical significance and that at least 12 paired samples would provide an 80% power to detect a 10% absolute difference in PMA from baseline at a significance level of 5%.…”

Section: Methodsmentioning

confidence: 99%

Cardiovascular effects of tumour necrosis factor α antagonism in patients with acute myocardial infarction: a first in human study

Padfield

Din

Koushiappi

et al. 2013

Heart

View full text Add to dashboard Cite

show abstract

“…22 Samples were not analyzed unless venesection achieved rapid and uninterrupted blood flow. Five minutes after sample collection, samples were stained with the following conjugated monoclonal antibodies: allophycocyanin-conjugated CD14, allophycocyanin-conjugated CD36, phycoerythrin-conjugated CD62P, and phycoerythrin-conjugated CD154; phycoerythrin-conjugated CD40, fluorescein isothiocyanate–conjugated CD42a, and appropriate control isotypes (all Becton Dickinson).…”

Section: Methodsmentioning

confidence: 99%

Fire Simulation and Cardiovascular Health in Firefighters

Hunter¹,

Shah²,

Langrish³

et al. 2017

Circulation

View full text Add to dashboard Cite

Background:Rates of myocardial infarction in firefighters are increased during fire suppression duties, and are likely to reflect a combination of factors including extreme physical exertion and heat exposure. We assessed the effects of simulated fire suppression on measures of cardiovascular health in healthy firefighters.Methods:In an open-label randomized crossover study, 19 healthy firefighters (age, 41±7 years; 16 males) performed a standardized training exercise in a fire simulation facility or light duties for 20 minutes. After each exposure, ex vivo thrombus formation, fibrinolysis, platelet activation, and forearm blood flow in response to intra-arterial infusions of endothelial-dependent and -independent vasodilators were measured.Results:After fire simulation training, core temperature increased (1.0±0.1°C) and weight reduced (0.46±0.14 kg, P<0.001 for both). In comparison with control, exposure to fire simulation increased thrombus formation under low-shear (73±14%) and high-shear (66±14%) conditions (P<0.001 for both) and increased platelet-monocyte binding (7±10%, P=0.03). There was a dose-dependent increase in forearm blood flow with all vasodilators (P<0.001), which was attenuated by fire simulation in response to acetylcholine (P=0.01) and sodium nitroprusside (P=0.004). This was associated with a rise in fibrinolytic capacity, asymptomatic myocardial ischemia, and an increase in plasma cardiac troponin I concentrations (1.4 [0.8–2.5] versus 3.0 [1.7–6.4] ng/L, P=0.010).Conclusions:Exposure to extreme heat and physical exertion during fire suppression activates platelets, increases thrombus formation, impairs vascular function, and promotes myocardial ischemia and injury in healthy firefighters. Our findings provide pathogenic mechanisms to explain the association between fire suppression activity and acute myocardial infarction in firefighters.Clinical Trial Registration:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01812317.

show abstract

“…Anti-platelet treatment reduces monocyte-platelet aggregation, a process thought to promote atherogenesis in patients with acute coronary syndrome. 23,[33][34][35][36] In addition to lowering cholesterol levels, life-saving statin therapy attenuates the production of inflammatory cytokines and coagulant factors and decreases the expression of cell adhesion molecules by circulating monocytes in hypercholesterolemic patients. [37][38][39] Angiotensin-converting enzyme inhibitors reduce tissue factor and serum levels of monocyte chemotactic protein 1 in patients after acute MI, 40 decelerating the coagulationinflammation-thrombosis cascade.…”

mentioning

confidence: 99%

Monocyte Fate in Atherosclerosis

Hilgendorf

Świrski

Robbins

2015

ATVB

161

113

View full text Add to dashboard Cite

Abstract-Monocytes and their descendant macrophages are essential to the development and exacerbation of atherosclerosis, a lipid-driven inflammatory disease. Lipid-laden macrophages, known as foam cells, reside in early lesions and advanced atheromata. Our understanding of how monocytes accumulate in the growing lesion, differentiate, ingest lipids, and contribute to disease has advanced substantially over the last several years. These cells' remarkable phenotypic and functional complexity is a therapeutic opportunity: in the future, treatment and prevention of cardiovascular disease and its complications may involve specific targeting of atherogenic monocytes/macrophages and their products.

show abstract

Clopidogrel reduces platelet-leucocyte aggregation, monocyte activation and RANTES secretion in type 2 diabetes mellitus

Cited by 32 publications

References 5 publications

Cardiovascular effects of tumour necrosis factor α antagonism in patients with acute myocardial infarction: a first in human study

Cardiovascular effects of tumour necrosis factor α antagonism in patients with acute myocardial infarction: a first in human study

Fire Simulation and Cardiovascular Health in Firefighters

Monocyte Fate in Atherosclerosis

Contact Info

Product

Resources

About