PAKing up to the endothelium

TL;DR

This paper reviews the role of Rac and PAK signaling pathways in endothelial cell functions during angiogenesis and discusses their potential as therapeutic targets for vascular-related diseases.

Contribution

It provides a comprehensive overview of Rac and PAK pathways in endothelial biology and highlights their therapeutic potential in controlling abnormal angiogenesis.

Findings

Rac and PAK modulate key endothelial processes like sprouting and migration.

Rac/PAK signaling influences vessel formation and maturation.

Targeting Rac/PAK pathways could normalize pathological angiogenesis.

Abstract

Angiogenesis recapitulates the growth of blood vessels that progressively expand and remodel into a highly organized and stereotyped vascular network. During adulthood, endothelial cells that formed the vascular wall retain their plasticity and can be engaged in neo-vascularization in response to physiological stimuli, such as hypoxia, wound healing and tissue repair, ovarian cycle and pregnancy. In addition, numerous human diseases and pathological conditions are characterized by an excessive, uncontrolled and aberrant angiogenesis. The signalling pathways involving the small Rho GTPase, Rac and its downstream effector the p21-activated serine/threonine kinase (PAK) had recently emerged as pleiotropic modulators in these processes. Indeed, Rac and PAK were found to modulate endothelial cell biology, such as sprouting, migration, polarity, proliferation, lumen formation, and maturation. Elucidating the Rac/PAK molecular circuitry will provide essential information for the development of new therapeutic agents designed to normalize the blood vasculature in human diseases.