Premium
Role of nuclear receptor signaling in platelets: antithrombotic effects of PPARβ
Author(s) -
Ali Ferhana Y.,
Davidson Simon J.,
Moraes Leonardo A.,
Traves Suzanne L.,
PaulClark Mark,
BishopBailey David,
Warner Timothy D.,
Mitchell Jane A.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.05-4395fje
Subject(s) - prostacyclin , nuclear receptor , peroxisome proliferator activated receptor , receptor , antithrombotic , platelet , platelet activation , chemistry , pharmacology , nitric oxide , endocrinology , medicine , microbiology and biotechnology , biochemistry , biology , transcription factor , gene
Peroxisome proliferator‐activated receptors (PPARs) are nuclear receptors that heterodimerize with the retinoid X receptor and then modulate at the transcriptional level the function of many target genes. Three PPARs are known: α, β (sometimes called δ), and γ. The better studied are PPARα and PPARγ, which are activated by fibrates and thiazolidinediones/glitazones, respectively. It is now believed that activation of the PPARs could be associated with the prevention of heart attack and stroke in humans. Here we report, for the first time, that human platelets contain PPARβ and that its selective activation inhibits platelet aggregation. PPARβ is a putative receptor for prostacyclin. Prostacyclin is an important antithrombotic hormone that synergizes with nitric oxide to inhibit platelet aggregation. In the current study, we show that PPARβ ligands similarly synergize with nitric oxide to inhibit platelet aggregation. These observations challenge our view of a nuclear receptor because PPARβ is present and active in nonnucleated platelets. Furthermore, these data suggest that some of the antithrombotic actions of prostacyclin may be mediated via activation of PPARs. Thus, our results identify PPARβ as a novel antiplatelet target that may mediate some of the effects of prostacyclin in blood.