Type

Journal Article

Authors

Paul Jurasz
Ian R Winship
Carlos A Velazquez-Martinez
Marek W Radomski
Maria-Jose Santos-Martinez
John M Seubert
Arno Siraki
Stephen Ogg
Ayman El-Kadi
Ahmed A El-Sherbeni
and 7 others

Subjects

Pharmacology

Topics
flow cytometry nitric oxide synthase human health blood platelets platelet aggregation matrix metalloproteinase 2 guanylate cyclase coronary artery disease

Differential eNOS-signalling by platelet subpopulations regulates adhesion and aggregation. (2016)

Abstract In addition to maintaining haemostasis, circulating blood platelets are the cellular culprits that form occlusive thrombi in arteries and veins. Compared to blood leucocytes, which exist as functionally distinct subtypes, platelets are considered to be relatively simple cell fragments that form vascular system plugs without a differentially regulated cellular response. Hence, investigation into platelet subpopulations with distinct functional roles in haemostasis/thrombosis has been limited. In our present study, we investigated whether functionally distinct platelet subpopulations exist based on their ability to generate and respond to nitric oxide (NO), an endogenous platelet inhibitor. Utilizing highly sensitive and selective flow cytometry protocols, we demonstrate that human platelet subpopulations exist based on the presence and absence of endothelial nitric oxide synthase (eNOS). Platelets lacking eNOS (approximately 20% of total platelets) fail to produce NO and have a down-regulated soluble guanylate cyclase-protein kinase G (sGC-PKG)-signalling pathway. In flow chamber and aggregation experiments eNOS-negative platelets primarily initiate adhesion to collagen, more readily activate integrin αIIbβ3 and secrete matrix metalloproteinase-2, and form larger aggregates than their eNOS-positive counterparts. Conversely, platelets having an intact eNOS-sGC-PKG-signalling pathway (approximately 80% of total platelets) form the bulk of an aggregate via increased thromboxane synthesis and ultimately limit its size via NO generation. These findings reveal previously unrecognized characteristics and complexity of platelets and their regulation of adhesion/aggregation. The identification of platelet subpopulations also has potentially important consequences to human health and disease as impaired platelet NO-signalling has been identified in patients with coronary artery disease.
Collections Ireland -> Trinity College Dublin -> PubMed

Full list of authors on original publication

Paul Jurasz, Ian R Winship, Carlos A Velazquez-Martinez, Marek W Radomski, Maria-Jose Santos-Martinez, John M Seubert, Arno Siraki, Stephen Ogg, Ayman El-Kadi, Ahmed A El-Sherbeni and 7 others

Experts in our system

1
Marek W Radomski
Trinity College Dublin
Total Publications: 44
 
2
Maria Jose Santos-Martinez
Trinity College Dublin
Total Publications: 29