Aggregation and Microparticle Production Through Toll-like Receptor 4 Activation in Platelets From Recently Menopausal Women
- 1 July 2009
- journal article
- research article
- Published by Wolters Kluwer Health in Journal of Cardiovascular Pharmacology
- Vol. 54 (1) , 57-62
- https://doi.org/10.1097/fjc.0b013e3181ab373d
Abstract
Bacterial infection may increase risk for thrombosis and atherosclerosis. Human platelets express toll-like receptor 4 (TLR4), the receptor for gram-negative bacterial lipopolysaccharide (LPS). Experiments were designed to evaluate direct, acute effects of TLR4 activation on aggregation, secretion, and generation of prothrombogenic microparticles in vitro on platelets derived from healthy women at risk for development of cardiovascular disease because of their hormonal status. Platelet-rich plasma from recently menopausal women was incubated with ultrapure Escherichia coli LPS in the absence or presence of antibodies that neutralize the human TLR4. Incubating platelets with LPS (100 ng/mL) for 5 minutes decreased aggregation and dense granule adenosine triphosphate secretion induced by thrombin receptor agonist peptide (TRAP) but not by adenosine diphosphate or collagen. The antibody to TLR4 blocked this effect of LPS. TLR4 activation increased phosphorylation of p38 mitogen-activated protein kinase and decreased production of prothrombotic phosphatidylserine and P-selectin-positive microparticles in response to TRAP. Therefore, acute, direct activation of TLR4 reduces platelet reactivity to TRAP stimulation in vitro. Increased thrombotic and cardiovascular risk with bacterial infection most likely reflects the sum of TLR4 activation on other blood and vascular cells to release proinflammatory cytokines/chemokines, which indirectly affect platelet reactivity.Keywords
This publication has 43 references indexed in Scilit:
- Shedding microvesicles: artefacts no morePublished by Elsevier ,2009
- Circulating microparticles and endogenous estrogen in newly menopausal womenClimacteric, 2009
- Characterization of blood borne microparticles as markers of premature coronary calcification in newly menopausal womenAmerican Journal of Physiology-Heart and Circulatory Physiology, 2008
- In vivo effects of lipopolysaccharide and TLR4 on platelet production and activity: implications for thrombotic riskJournal of Applied Physiology, 2007
- Circulating MicroparticlesHypertension, 2006
- Differential effects of 17β-estradiol, conjugated equine estrogen, and raloxifene on mRNA expression, aggregation, and secretion in plateletsAmerican Journal of Physiology-Heart and Circulatory Physiology, 2005
- Evidence of Toll‐like receptor molecules on human plateletsImmunology & Cell Biology, 2005
- Potential Role of Endotoxin as a Proinflammatory Mediator of AtherosclerosisArteriosclerosis, Thrombosis, and Vascular Biology, 2004
- C-Reactive protein levels among women of various ethnic groups living in the United States (from the Women's Health Study)The American Journal of Cardiology, 2004
- Mechanisms of the priming effect of low doses of lipopolysaccharides on leukocyte-dependent platelet aggregation in whole bloodThrombosis and Haemostasis, 2003