Endothelial cell apoptosis in angiogenesis and vessel regression

Abstract

Blood vessel regression is an essential process for ensuring blood vessel networks function at optimal efficiency and for matching blood supply to the metabolic needs of tissues as they change over time. Angiogenesis is the major mechanism by which new blood vessels are produced, but the vessel growth associated with angiogenesis must be complemented by remodeling and maturation events including the removal of redundant vessel segments and cells to fashion the newly forming vasculature into an efficient, hierarchical network. This review will summarize recent findings on the role that endothelial cell apoptosis plays in vascular remodeling during angiogenesis and in vessel regression more generally.

Keywords: BCL2; Death receptors; Diabetes; Diabetic retinopathy; Vessel pruning.

Fig. 1

Schematic overview of the BCL2-regulated and death receptor-regulated apoptosis pathways. In the BCL2 pathway, interactions between opposing factions of BCL2 family proteins (pro-apoptotic BH3-only sub-family proteins and pro-survival BCL2 sub-family proteins) determine whether the effector sub-family proteins BAK and BAX become activated. Activation of BAK and BAX results in mitochondrial permeability and release of apoptogenic factors such as cytochrome C, which, in turn, leads to activation of the caspase cascade via caspase 9. In the extrinsic pathway, death receptor-ligand engagement by their cognate receptor leads to activation of the caspase cascade via caspase 8. In some cell types, caspase 8 cleaves the BH3-only protein BID, yielding its active, truncated form (tBID) that can activate BAX and BAK

Fig. 2

Overview of selected endothelial cell survival signaling pathways. EC survival is regulated via multiple signaling pathways, including growth factor receptor tyrosine kinases, G-protein coupled receptors, and mechanical forces, such as laminar blood flow shear stress. See main text for details