Smoke exposed mice had lower amount of Vegfa expression as well (Fig. 5, p-value of the t-test = 4.0×10−7 and 0.01 for the C57BL/6J and A/J smoking models, respectively), which suggests that Epas1 downstream target genes were down regulated in the smoke exposed mice at the time when emphysema develops in these models. This evidence concerns the gene EPAS1 and pulmonary emphysema.