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Antithrombotic actions of statins involve PECAM-1 signalling

Moraes, L. A., Vaiyapuri, S., Sasikumar, P., Ali, M. S., Kriek, N. K., Sage, T. and Gibbins, J. M. (2013) Antithrombotic actions of statins involve PECAM-1 signalling. Blood, 122 (18). pp. 3188-3196. ISSN 0006-4971

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To link to this item DOI: 10.1182/blood-2013-04-491845

Abstract/Summary

Statins are widely prescribed cholesterol-lowering drugs that are a first-line treatment for coronary artery disease and atherosclerosis, reducing the incidence of thrombotic events such as myocardial infarction and stroke. Statins have been shown to reduce platelet activation, although the mechanism(s) through which this occurs is unclear. Since several of the characteristic effects of statins on platelets are shared with those elicited by the inhibitory platelet adhesion receptor PECAM-1, we investigated a potential connection between the influence of statins on platelet function and PECAM-1 signalling. Statins were found to inhibit a range of platelet functional responses and thrombus formation in vitro and in vivo. Notably, these effects of statins on platelet function in vitro and in vivo were diminished in PECAM-1-/- platelets. Activation of PECAM-1 signalling results in its tyrosine phosphorylation, the recruitment and activation of tyrosine phosphatase SHP-2, the subsequent binding of phosphoinositol 3-kinase (PI3-K) and diminished PI3-K signalling. Statins resulted in the stimulation of these events, leading to the inhibition of Akt activation. Together, these data provides evidence for a fundamental role of PECAM-1 in the inhibitory effects of statins on platelet activation, which may explain some of the pleiotropic actions of these drugs.

Item Type:Article
Refereed:Yes
Divisions:Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
Faculty of Life Sciences > School of Biological Sciences > Biomedical Sciences
ID Code:34247
Uncontrolled Keywords:platelets, thrombosis, haemostasis, statins, PECAM
Additional Information:Freely available from publisher's website and PMC. See links.
Publisher:American Society of Hematology

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