ERK and Smads: Getting together for angiogenic sprouting

Abstract

See article by Zhou et al. [8] (pages 390–399) in this issue. Sprouting of new blood vessels from preexisting capillaries is a multi-faceted and highly orchestrated process that is dependent on a finely tuned balance between pro-angiogenic and anti-angiogenic microenvironmental clues [1]. Perturbations in the equilibrium between pro-angiogenic and anti-angiogenic factors can lead to excessive or defective vascularization [1,2]. Inputs from the microenvironment impinge upon receptive endothelial cells to initiate a multi-step response characterized by degradation of the basement membrane, sprout formation, proliferation, migration along the sprouts and organization into a tubular network of vascular-like structures that ultimately, with the recruitment of mural cells, acquire the anatomical and functional characteristics of mature blood vessels [1]. Microenvironmental clues originating from angiogenic protein and lipid growth factors, tissue oxygenation, adjacent cells, or components of the extracellular matrix are processed by the endothelial cells via intracellular and intercellular signaling pathways that are temporally and spatially segregated to coordinate the initiation, progression and completion of each stage of the angiogenic response [1,3,4]. These signaling pathways, rather than following a linear path, are organized via a cascade of signaling molecules, scaffolding proteins and multi-domain adaptor proteins into highly interconnected networks that provide endothelial cells with a myriad of opportunities for signal integration and crosstalk [5–7]. … *Signal Transduction Laboratory, Methodist Research Institute, Clarian Health Partners, 1800 N. Capitol Blvd, Noyes Bldg, Room E504, Indianapolis, IN, 46202, USA. Tel.: +1 317 962 6891; fax: +1 317 962 9369. mrizzo{at}clarian.org