Modulation of Bone Marrow-Derived Endothelial Progenitor Cell Activity by Protein Tyrosine Phosphatases

Adult bone marrow contains stem cells capable of reconstituting the vascular system. The ordered progression of stem cells and more differentiated endothelial precursor cells through successive developmental stages is tightly controlled. The specialized microenvironment of the bone marrow as well as cell-autonomous processes directs the renewal and differentiation of stem cells into endothelial cells. Tyrosine phosphorylation of receptors, adaptors, and structural proteins is one mechanism whereby endothelial cell development is regulated, which involves the opposing action of protein tyrosine kinases and phosphatases. The present review focuses on the role of four nontransmembrane protein tyrosine phosphatases (TC-PTP, PTP1B, SHP-1, and SHP-2) in the self-renewal, differentiation, mobilization, and homing of endothelial progenitor cells, as well as their ability to incorporate into nascent blood vessels. Endothelial progenitor cells are known to promote vasculogenesis, accelerating restoration of blood flow to ischemic tissues, and improve cardiac function after infarct. The use of protein tyrosine phosphatase inhibitors to modulate the development and function of endothelial progenitor cells as a potential novel therapy for peripheral vascular and coronary artery disease in humans is discussed.