Thymosin β4 and the vasculature: multiple roles in development, repair and protection against disease.

Introduction: Formation of the vasculature is a complex process, defects in which can lead to embryonic lethality or disease in later life. Understanding mechanisms of vasculogenesis may facilitate the treatment of developmental defects and may be extrapolated to promote wound healing and tissue repair. Thymosin 4 (T4) is an actin monomer binding protein with recognized roles in vascular development, neovascularization and protection against disease.Areas covered: Vascular network assembly is complex, regulated by multiple signals and cell types; T4 functions in many of the underlying processes, including vasculogenesis, angiogenesis, arteriogenesis, endothelial-mesenchymal transition and extracellular matrix remodeling. Loss of T4 perturbs vessel growth and stability, whereas exogenous application enhances capillary formation and pericyte recruitment, during development and in injury models.Expert opinion: Although vascular functions for T4 have been well documented, the underlying molecular mechanisms remain obscure. While T4-induced cytoskeletal remodeling likely mediates the directional migration of endothelial cells, paracrine roles have also been implicated in migration and differentiation of smooth muscle cells. Moreover, nuclear functions of T4 have been described but remain to be explored in the vasculature. Delineati+ng the molecular pathways impacted by T4 to promote vascular growth and remodeling may reveal novel targets for prevention and treatment of vascular disease.