Cardiothoracic Pharmacology, National Heart and Lung Institute, Imperial College London, London, UK.
Arterioscler Thromb Vasc Biol. 2009 Nov;29(11):1871-3. doi: 10.1161/ATVBAHA.109.193367. Epub 2009 Aug 20.
Peroxisome proliferator-activated receptor beta/delta (PPARbeta/delta) is a nuclear receptor found in platelets. PPARbeta/delta agonists acutely inhibit platelet function within a few minutes of addition. As platelets are anucleated, the effects of PPARbeta/delta agonists on platelets must be nongenomic. Currently, the particular role of PPARbeta/delta receptors and their intracellular signaling pathways in platelets are not known.
We have used mice lacking PPARbeta/delta (PPARbeta/delta(-/-)) to show the effects of the PPARbeta/delta agonist GW501516 on platelet adhesion and cAMP levels are mediated specifically by PPARbeta/delta, however GW501516 had no PPARbeta/delta-specific effect on platelet aggregation. Studies in human platelets showed that PKCalpha, which can mediate platelet activation, was bound and repressed by PPARbeta/delta after platelets were treated with GW501516.
These data provide evidence of a novel mechanism by which PPAR receptors influence platelet activity and thereby thrombotic risk.
过氧化物酶体增殖物激活受体β/δ（PPARβ/δ）是血小板中发现的核受体。PPARβ/δ激动剂在添加后几分钟内即可急性抑制血小板功能。由于血小板无核，因此 PPARβ/δ激动剂对血小板的作用必须是非基因组的。目前，PPARβ/δ受体及其在血小板中的细胞内信号通路的特定作用尚不清楚。
我们使用缺乏 PPARβ/δ（PPARβ/δ（-/-））的小鼠表明，PPARβ/δ激动剂 GW501516 对血小板黏附和 cAMP 水平的影响是由 PPARβ/δ特异性介导的，但是 GW501516 对血小板聚集没有 PPARβ/δ特异性作用。在人类血小板中的研究表明，PKCalpha 可以介导血小板激活，在用 GW501516 处理血小板后，PPARβ/δ 结合并抑制了 PKCalpha。
这些数据提供了证据，表明 PPAR 受体通过影响血小板活性从而影响血栓形成风险的一种新机制。
