A study shows that chronic inhibition of VEGF receptors leads to alveolar cell apoptosis and emphysema in rats. The VEGF receptor inhibitor SU5416 caused enlargement of air spaces, indicating emphysema, and induced alveolar septal cell apoptosis without inhibiting lung cell proliferation. Angiography revealed pruning of the pulmonary arterial tree, but no inflammatory cell infiltration or fibrosis. SU5416 treatment reduced lung expression of VEGF receptor 2 (VEGFR-2), phosphorylated VEGFR-2, and Akt-1. The caspase inhibitor Z-Asp-CH₂-DCB prevented SU5416-induced apoptosis and emphysema. These findings suggest that VEGF receptor signaling is essential for maintaining alveolar structures, and alveolar septal cell apoptosis contributes to emphysema pathogenesis. The study also shows that SU5416 treatment caused increased caspase 3-like activity and apoptosis in lung cells, while the caspase inhibitor reduced these effects. The results indicate that VEGF receptor signaling is crucial for lung alveolar structure maintenance, and its disruption leads to apoptosis and emphysema. The study highlights the role of apoptosis in emphysema development and suggests that targeting apoptosis may offer new therapeutic strategies for emphysema.A study shows that chronic inhibition of VEGF receptors leads to alveolar cell apoptosis and emphysema in rats. The VEGF receptor inhibitor SU5416 caused enlargement of air spaces, indicating emphysema, and induced alveolar septal cell apoptosis without inhibiting lung cell proliferation. Angiography revealed pruning of the pulmonary arterial tree, but no inflammatory cell infiltration or fibrosis. SU5416 treatment reduced lung expression of VEGF receptor 2 (VEGFR-2), phosphorylated VEGFR-2, and Akt-1. The caspase inhibitor Z-Asp-CH₂-DCB prevented SU5416-induced apoptosis and emphysema. These findings suggest that VEGF receptor signaling is essential for maintaining alveolar structures, and alveolar septal cell apoptosis contributes to emphysema pathogenesis. The study also shows that SU5416 treatment caused increased caspase 3-like activity and apoptosis in lung cells, while the caspase inhibitor reduced these effects. The results indicate that VEGF receptor signaling is crucial for lung alveolar structure maintenance, and its disruption leads to apoptosis and emphysema. The study highlights the role of apoptosis in emphysema development and suggests that targeting apoptosis may offer new therapeutic strategies for emphysema.