LXR as a novel antithrombotic target.

Abstract:

:Liver X receptors (LXRs) are transcription factors involved in the regulation of cholesterol homeostasis. LXR ligands have athero-protective properties independent of their effects on cholesterol metabolism. Platelets are involved in the initiation of atherosclerosis and despite being anucleate express nuclear receptors. We hypothesized that the athero-protective effects of LXR ligands could be in part mediated through platelets and therefore explored the potential role of LXR in platelets. Our results show that LXR-β is present in human platelets and the LXR ligands, GW3965 and T0901317, modulated nongenomically platelet aggregation stimulated by a range of agonists. GW3965 caused LXR to associate with signaling components proximal to the collagen receptor, GPVI, suggesting a potential mechanism of LXR action in platelets that leads to diminished platelet responses. Activation of platelets at sites of atherosclerotic lesions results in thrombosis preceding myocardial infarction and stroke. Using an in vivo model of thrombosis in mice, we show that GW3965 has antithrombotic effects, reducing the size and the stability of thrombi. The athero-protective effects of GW3965, together with its novel antiplatelet/thrombotic effects, indicate LXR as a potential target for prevention of athero-thrombotic disease.

journal_name

Blood

journal_title

Blood

authors

Spyridon M,Moraes LA,Jones CI,Sage T,Sasikumar P,Bucci G,Gibbins JM

doi

10.1182/blood-2010-09-306142

subject

Has Abstract

pub_date

2011-05-26 00:00:00

pages

5751-61

issue

21

eissn

0006-4971

issn

1528-0020

pii

blood-2010-09-306142

journal_volume

117

pub_type

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