It Is Proposed That Cardiovascular Functions are Regulated by the Status of Ecto-phosphoproteins Orchestrated by Platelets

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.