Regulation of Angiogenesis and Vascular Remodeling by Endothelial Akt Signaling

Abstract

Since the initial identification of several classes of receptor tyrosine kinases and their ligands as crucial mediators of vascular development, considerable progress has been made toward understanding the process of angiogenesis at sites of tissue growth and/or repair (1,2). A number of clinical trials are currently evaluating angiogenic ligands for their ability to induce neovascularization in ischemic tissues (3,4), and the intracellular signaling pathways that mediate the proangiogenic effects of these growth factors are being extensively investigated. Among a number of signaling pathways activated by angiogenic growth factors, the phosphoinositide 3-kinase (PI3K)/Akt pathway is of particular interest because it regulates downstream target molecules that are potentially involved in blood vessel growth and homeostasis, and thus seems to be a major mediator that couples “inputs” with “outputs” in the endothelium.