Abstract
Platelets are at the nexus of virtually all physiological processes that occur within
the cardiovascular system. The inordinate number and variety of platelet surface receptors
allow these anucleate cells to interact with and respond to all the cell types in
the blood, the vast vascular endothelial cell lining, the subendothelial matrix, foreign
antigens/pathogens, and soluble plasma components from simple inorganic molecules,
like Ca+2, to some of the most complex macromolecules, like von Willebrand factor. The surface
receptors are but one component of the platelet's armory that regulates cardiovascular
functions. Upon activation, platelets release 100s of different molecules from dense
granules, α-granules, lysosomes, and from nongranule sources. The releasate contains
a host of bioreactive molecules, including cytokines, chemokines, and growth factors
required for normal and pathological cardiovascular functions. Also, among the released
components are high concentrations of ATP along with soluble and extracellular membrane-bound
protein kinases and likely protein phosphatases. The platelet is exquisitely poised
to react to extracellular signals that alter intracellular pathways (“outside-in signaling”)
resulting in the dramatic shape change from discoid to an enlarged amorphous cell
that culminates in the direct interaction with other platelets, subendothelial matrixes,
and other cell types. At the same time, the released platelet components are ideally
suited to support the phosphorylation of protein players involved in a myriad of extracellular
pathways within the microenvironment where platelets are activated. This paper presents
scenarios where ecto-phospho-/dephosphorylated-proteins are known to or could regulate
physiological processes in the cardiovascular system associated with atherogenesis
and cardiovascular diseases.
Keywords
cardiovascular disease - platelets - ecto-protein kinase - extracellular phosphorylation
