Increased platelet activation and thrombosis in transgenic mice expressing constitutively active P2Y12.

ABSTRACT:

Background

In our previous in vitro study, we reported a constitutively active chimeric P2Y(12) (cP2Y(12)) and found that AR-C78511 is a potent inverse agonist at this receptor. The role of cP2Y(12) in platelet activation and thrombosis is not clear.

Objectives

To investigate the physiologic implications of cP2Y(12) for platelet activation and thrombus formation, and to evaluate the antiplatelet activity of AR-C78511 as an inverse agonist.

Methods and results

We generated transgenic mice conditionally and platelet-specifically expressing cP2Y(12). High-level expression of cP2Y(12) in platelets increased platelet reactivity, as shown by increased platelet aggregation in response to multiple platelet agonists. Moreover, transgenic mice showed a shortened bleeding time,

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC3495164 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature