Abstract
It is currently accepted that cGMP-dependent protein kinase (PKG) inhibits platelet activation. Here, we show that PKG plays an important stimulatory role in platelet activation. Expression of recombinant PKG in a reconstituted cell model enhanced von Willebrand factor (vWF)-induced activation of the platelet integrin αIIbβ3. PKG knockout mice showed impaired platelet responses to vWF or low doses of thrombin and prolonged bleeding time. Human platelet aggregation induced by vWF or low-dose thrombin was inhibited by PKG inhibitors but enhanced by cGMP. Furthermore, a cGMP-enhancing agent, sildenafil, promoted vWF- or thrombin-induced platelet aggregation. The cGMP-stimulated platelet responses are biphasic, consisting of an initial transient stimulatory response that promotes platelet aggregation and a subsequent inhibitory response that limits the size of thrombi.
| Original language | English |
|---|---|
| Pages (from-to) | 77-86 |
| Number of pages | 10 |
| Journal | Cell |
| Volume | 112 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 10 2003 |
Bibliographical note
Funding Information:We thank Drs. C. Ruan and M.C. Berndt for providing reagents, and Drs. M.C. Berndt, P. Newman, and many other colleagues for critical reading of various versions of the manuscript. This work was supported in part by grants from the NHLBI/NIH, HL62350, and HL68819, and by a Grant-in Aid from AHA. Z.L. is supported by a fellowship award from the American Heart Association Midwest Affiliate.
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology