Vascular Endothelial Growth Factor in Idiopathic Pulmonary Fibrosis. An Imbalancing Act

Limited and controversial published data suggest that VEGF-A, often denoted simply as VEGF, may have both pathology-driving and protective functions in various lung diseases, including pulmonary fibrosis (3-7), and one of the approved therapeutics for IPF, nintedanib, acts by targeting VEGF receptor signaling in combination with inhibiting fibroblast growth factor receptor and platelet-derived growth factor receptor activities (8). On the basis of their abundant results, the authors concluded that VEGFxxxa isoforms are profibrotic, whereas VEGF165b inhibits fibrosis. [...]an imbalance of VEGF splice isoforms appears to be an important contributor to the pathogenesis of IPF, whereas its rebalancing may hold therapeutic promise for this enigmatic disease. Perhaps the greatest is the integration of diverse and well-controlled data obtained at various levels of complexity, including at the molecular, cellular, and organismal levels. [...]the results are both directly disease related and revealing of pathophysiologic mechanisms. Vascular endothelial growth factor (VEGF) in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS): paradox or paradigm?