Abbreviations: CSE = cigarette smoke extract;
VEGF = vascular endothelial cell growth factor.
mechanisms behind the disappearance of lung tissue (“vanishing
lung”) in COPD remain enigmatic in spite of the commonly discussed
hypotheses of lung inflammation and a protease-antiprotease imbalance.
We postulate that there are cellular and molecular programs that
maintain the structure of the adult lung. One or several of such lung
cell maintenance programs, in particular for lung endothelial cells, is
disrupted by the toxic effect of chronic cigarette smoke in genetically
susceptible patients, thus resulting in centrilobular emphysema.
Specifically, we hypothesize that disappearance of lung alveoli
resulting in centrilobular emphysema occurs by apoptosis after
decreased expression or activity of lung vascular endothelial cell
growth factor (VEGF) or its receptors due to smoking. In the present
work, we focused on the effect of cigarette smoke extract (CSE) on VEGF
gene expression, on endothelial cell apoptosis, and on the ratio of the
transcription factors Sp1 and Sp3, which are involved in the regulation
of VEGF receptor kinase domain receptor expression in endothelial