p38 MAP kinase—a molecular switch between VEGF-induced angiogenesis and vascular hyperpermeability

SPECIFIC AIMSA dissection of molecular pathways between VEGF-induced angiogenesis and vascular permeability would be desirable for the development of angiogenic and anti-angiogenic therapies. Therefore, our specific objective was to investigate the role of the p38 MAPK as the signaling molecule that separates these two processes.PRINCIPAL FINDINGS1. p38 MAPK has a negative regulatory role in VEGF-induced angiogenesisTo analyze the involvement of VEGF-induced p38 MAPK activation in angiogenesis, we assessed an in vitro assay for endothelial sprout formation. VEGF strongly induced sprout formation in primary human microvascular lung endothelial cells (HLMEC). Inhibition of the p38 MAPK by two small chemical inhibitors (SB203580 and SB202190) led to a more than additive increase in the number of sprouts, indicating a negative regulatory role of the p38 MAPK in this model of sprouting angiogenesis (Fig. 1⤻ A). This finding was not restricted to microvascular endothelial cells from the lung, since an enhanceme...