VEGF levels in the alveolar compartment do not distinguish between ARDS and hydrostatic pulmonary oedema

Abstract

Although overexpression of vascular endothelial growth factor (VEGF) 165 in the lung causes pulmonary oedema, its role in human acute lung injury (ALI) is unclear. VEGF levels are reported to be lower in bronchoalveolar lavage from ALI patients compared with normals, but these studies did not include a comparably ill control group with noninflammatory pulmonary oedema.The current authors hypothesised that VEGF levels in pulmonary oedema fluid would be lower in ALI patients compared with control patients with severe hydrostatic pulmonary oedema. VEGF was measured in pulmonary oedema fluid and plasma from 56 patients with ALI and 46 controls with severe hydrostatic pulmonary oedema.Pulmonary oedema fluid levels of VEGF did not differ between patients with hydrostatic oedema (median 799 pg?mL -1 , interquartile range (IQR) 226-2,281) and ALI (median 507, IQR 0.8-1,031).Plasma levels were also the same (median 20.5 pg?mL -1 , IQR 0-152 versus 4.8, IQR 0-99.8). There was no association between plasma or oedema fluid VEGF levels and outcomes including mortality. Vascular endothelial growth factor levels in pulmonary oedema fluid were depressed both in acute lung injury and hydrostatic pulmonary oedema. The decrease in air space concentrations of vascular endothelial growth factor in acute lung injury may not be a function of the degree of lung injury, but rather may result from alveolar flooding.

Magnitude-dependent effects of cyclic stretch on HGF- and VEGF-induced pulmonary endothelial remodeling and barrier regulation

“…Under conditions of stress or injury, such as in ALI or VILI, because of the anatomic proximity between alveolar epithelial and microvascular ECs, VEGF may literally spill onto the pulmonary ECs, increasing permeability and leading to interstitial and pulmonary edema (25,43). VEGF increases in the lung have been shown in various lung pathologies including hydrostatic edema, ARDS, and LPS-induced lung injury (28,69). In addition, high tidal volume ventilation may stimulate VEGF expression, and VEGF release by other organs (kidney and liver) contributes to VILI-related multiorgan failure (22).…”

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

“…This may explain why the expression of VEGF in ALI varies among animal models 35,36 and in patients at different clinical stages. 13,14,17,37,38 Overexpression of VEGF or inhibition of VEGF with chemical inhibitors or soluble decoy receptors can show the overall role of VEGF, but cannot dissect the contribution of VEGF from different cell types. Type II cells produce VEGF in vitro 39 and are a source of expression of VEGF protein 40 and mRNA 41 in the adult lung.…”

“…6 In addition, VEGF levels in the alveolar compartment of patients with ARDS are indistinguishable from those in patients with hydrostatic pulmonary edema. 13 Lung epithelial lining fluid from ARDS patients actually contained lower levels of VEGF than that from at-risk subjects, and increased levels at Day 4 were associated with better recovery.…”

Dopamine inhibits pulmonary edema through the VEGF-VEGFR2 axis in a murine model of acute lung injury

“…We now provide evidence that the same mechanisms operate in murine endotoxin-induced ALI and can be targeted to improve morbidity and mortality in this preclinical model. Sepsis is the most common cause of ALI in humans (50,51). Administration of the gram-negative bacterial endotoxin lipopolysaccharide (LPS) has been widely used as an animal model of sepsis-related lung injury.…”

“…dopamine receptor D2; vascular endothelial growth factor ACUTE LUNG INJURY (ALI) and its severe form, the acute respiratory distress syndrome (ARDS), are prevalent causes of morbidity and mortality (51). One of the hallmarks of ALI is the accumulation of protein-rich alveolar edema fluid resulting from impaired vascular barrier properties (29,33,50,53). Not only are vascular filtration coefficient and protein permeability increased, injured lungs are also defective in alveolar fluid clearance (35,52).…”