Rho guanine exchange factors in blood vessels: Fine-tuners of angiogenesis and vascular function

The angiogenic cascade is a multi-step process essential for embryogenesis and other physiological and pathological processes. Rho family GTPases are binary molecular switches and serve as master regulators of various basic cellular processes. Rho GTPases are known to exert important functions in angiogenesis and vascular physiology. These functions demand a tight and context-specific control of cellular processes requiring superordinate control by a multitude of guanine nucleotide exchange factors (GEFs). GEFs display various features enabling them to fine-tune the actions of Rho GTPases in the vasculature: (1) GEFs regulate specific steps of the angiogenic cascade; (2) GEFs show a spatio-temporally specific expression pattern; (3) GEFs differentially regulate endothelial function depending on their subcellular location; (4) GEFs mediate crosstalk between complex signaling cascades and (5) GEFs themselves are regulated by another layer of interacting proteins. The aim of this review is to provide an overview about the role of GEFs in regulating angiogenesis and vascular function and to point out current limitations as well as clinical perspectives.

► Rho GTPases are master regulators of the angiogenic cascade.
► GEFs regulate Rho GTPases depending on the cellular context.
► GEFs are critical for angiogenesis and blood vessel function.
► We discuss five characteristic features displayed by GEFs in the vasculature.
► GEFs are potential drug targets and further investigation may be promising.