VEGF in the lung: a role for novel isoforms

Area of Science:

• Pulmonary Medicine
• Molecular Biology
• Cell Biology

Background:

• Vascular endothelial growth factor (VEGF) plays a critical role in lung physiology and disease.
• Elevated plasma VEGF and decreased alveolar VEGF in acute respiratory distress syndrome (ARDS) create controversy regarding VEGF's function.
• The anti-angiogenic VEGF-b family may influence VEGF bioactivity in the lung.

Purpose of the Study:

• To investigate the expression and function of the anti-angiogenic VEGF-b family in normal and ARDS lung tissue.
• To determine the effect of VEGF-b on endothelial and alveolar epithelial cell proliferation.

Main Methods:

• Immunohistochemistry and immunoblotting were used to assess VEGF-b protein expression in lung tissue, alveolar cells, and bronchoalveolar lavage (BAL) fluid.
• ELISA quantified VEGF-b levels in normal,
• at risk,
• and ARDS subjects.
• [(3)H]thymidine uptake assays measured the proliferative effects of VEGF(165) and VEGF(165)b on human endothelial and alveolar epithelial cells.

Main Results:

• VEGF(165)b was abundant in normal lung tissue but decreased in ARDS lung.
• VEGF(121)b and VEGF(165)b were detected in lung tissue, BAL fluid, and alveolar type II (ATII) cell lysates.
• VEGF(165)b significantly inhibited the proliferative effects of VEGF(165) on both endothelial and alveolar epithelial cells (P < 0.01).

Conclusions:

• The anti-angiogenic VEGF-b family is expressed in normal lungs and reduced in ARDS.
• VEGF-b demonstrates functional effects on human endothelial and alveolar epithelial cells.
• The VEGF-b family may play a crucial role in lung injury repair mechanisms.