Platelets: developmental biology, physiology, and translatable platforms for preclinical investigation and drug development.
This paper, developed from the proceedings of the 2007 Platelet Colloquium, considers emerging constructs in platelet biology, preclinical models of thrombosis, and their potential application to the development of platelet-directed pharmacotherapies. Discussed first is the developmental biology of platelets, including megakaryocyte maturation, and the role of apoptotic and growth factors and other proteins in thrombopoiesis. A brief overview of current methods and observations from platelet proteomic analyses is also presented, illustrating the complex interplay of genes, gene expression, protein expression, and protein modification in various atherothrombotic phenotypes. The factor Xa-platelet interface is used as a working model for discussion of anticoagulants as platelet antagonists, highlighting the importance of receptor expression, substrate binding kinetics, platelet subpopulations, and cofactors in thrombosis. Finally, we discuss the use of emerging technologies--such as intravital microscopy and ex vivo perfusion chambers--as translatable platforms for investigating the role of platelets and their pharmacologic inhibition in human health and disease.
Methodist DeBakey Heart Center, Houston, Texas, USA.
Neal S
NS
Kleiman
Jane E
JE
Freedman
Paula B
PB
Tracy
Barbara C
BC
Furie
Paul F
PF
Bray
Sunil V
SV
Rao
David R
DR
Phillips
Robert F
RF
Storey
Christopher P
CP
Rusconi
Patricia A
PA
French
Steven R
SR
Steinhubl
Richard C
RC
Becker
D000818:Animals; D001792:Blood Platelets / Q000737:chemistry / Q000166:cytology* / Q000502:physiology; D015195:Drug Design; D020869:Gene Expression Profiling; D006801:Humans; D040901:Proteomics; D013927:Thrombosis / Q000188:drug therapy / Q000209:etiology