Vascular endothelial growth factor and related molecules in acute lung injury

Abstract

VEGFs and their receptors have been implicated in the regulation of vascular permeability in many organ systems, including the lung. Increased permeability and interstitial and pulmonary edema are prominent features of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Extrapolating data from other organ systems and animal experiments have suggested that overexpression of VEGF functions primarily as proinjurious molecules in the lung. Recent data, from animal models as well as from patients with ARDS, have shown decreased levels of VEGF in the lung. The role of VEGF and related molecules in ALI/ARDS is, therefore, controversial: what has become clear is that there are many unique features in the regulation of pulmonary vascular permeability and in VEGF expression in the lung. In this review, we explore a growing body of literature looking at the expression and function of VEGF and related molecules in different models of ALI and in patients with ALI/ARDS. Novel evidence points to a potential role of VEGF in promoting repair of the alveolar-capillary membrane during recovery from ALI/ARDS. Understanding the role of VEGF in this disease process is crucial for developing new therapeutic strategies for ALI/ARDS.

Genome-wide analysis of DNA methylation in rat lungs with lipopolysaccharide-induced acute lung injury

“…ALI/ARDS is characterized by alveolar injury and increased pulmonary vascular permeability. Mura et al (22) reported a potential role for VEGF in promoting the repair of the alveolar-capillary membrane during recovery from ALI/ARDS. Vegfb is associated with the VEGF signaling pathway and is involved in the promotion of angiogenesis.…”

Functions of Type II Pneumocyte-Derived Vascular Endothelial Growth Factor in Alveolar Structure, Acute Inflammation, and Vascular Permeability

“…VEGF is a well-known vascular permeability factor. 1,9,47 VEGF can reduce transendothelial electrical resistance, induce endothelial migration 5 as well as phosphorylation of VE-cadherin and E-cadherin, and alter the actin stress fibers in pulmonary endothelial cells. 6 Using a ventilated pulmonary ischemia model in isolated ferret lungs, it has been shown that pulmonary vascular barrier dysfunction is associated with a rapid increase in VEGF expression.…”

“…Moreover, the chemotactic activity of VEGF may contribute to monocyte activation and migration. 9 Lack of type II epithelial cell-derived VEGF may reduce the recruitment of inflammatory cells into the lung. Our results strongly support the hypothesis that VEGF locally produced in the distal lung epithelial cells is important for the pathogenesis of ALI/ARDS.…”

Control of lung vascular permeability and endotoxin-induced pulmonary oedema by changes in extracellular matrix mechanics

“…10), among others. Indeed, the levels of these chemical factors are elevated in lung epithelial lining fluid collected from patients with early phase of ARDS, and they seem to have a key role in the pathogenesis of this disease 11,12 . The present study was initiated based on the recent finding that VEGF-induced angiogenesis can be regulated by changes in the mechanical properties (for example, physical compliance) of the extracellular matrix (ECM), which also has a central role in control of stem cell fate switching and tissue development, as well as cancer formation [13][14][15][16] .…”