Inhibition of VEGF receptors causes lung cell apoptosis and emphysema

Pulmonary Epithelial Neuropilin-1 Deletion Enhances Development of Cigarette Smoke–induced Emphysema

“…Published literature describes spontaneous airspace enlargement in mice that are conditionally deficient for VEGF (71) or components of other growth factor signaling cascades that are active during normal lung development (72)(73)(74)(75)(76). Additional studies demonstrate that dysregulation of programmed cell death in the adult lung may lead to airspace enlargement in the absence of marked inflammation (39,46,77,78). It was also shown that alteration of genes associated with cellular senescence, a state characterized by impaired recovery from injury, may sensitize mice to CS-induced inflammation and emphysema (54).…”

“…Augmented apoptosis (39,44,46) and attenuated proliferation (56,57) of alveolar cells were shown to be critical for the maintenance of normal alveolar structure in other animal models of emphysema. Evidence suggests that high levels of Nrp1 may attenuate apoptosis (58).…”

“…Nrp1 may modulate the balance between VEGF and Sema3 signaling to alter cell proliferation and death in nonepithelial cell types (17,26). Both Nrp1 ligands, VEGF, and Sema3A, have independently been shown to contribute to alveolar septation (24,(27)(28)(29)(30) and vascular patterning (23,27,31), and human (32,33), animal (34)(35)(36)(37), and in vitro (38) studies support a possible role for VEGF in protection from acute lung injury and preservation of alveolar cell survival (39). Of note, it was shown that expression of Nrp1 protein was reduced in the lungs from smokers with spirometric evidence of COPD compared with smokers who had normal lung function and nonsmoking control subjects (40).…”

Prostaglandin E2 possesses different potencies in inducing Vascular Endothelial Growth Factor and Interleukin-8 production in COPD human lung fibroblasts

“…Cigarette smoke, the major risk factor of COPD, also promotes the induction of COX-2 and PGE 2 receptor expression in neutrophils and alveolar macrophages (AM), therefore contributing to the proinflammatory effects of PGE 2 in the airways of COPD subjects [24,26]; indeed a significant overlap with minor, but statistically significant, differences was observed between HS and COPD subjects in terms of COX-2 and PGE 2 , but clearcut increases, in agreement with previously published data [27], were observed in COPD subjects only for EP2 and EP4 expressions, both as mRNA and protein, suggesting that the increase in PGE 2 -dependent IL-8 formation may be the result of concomitant higher PGE2 concentration and enhanced receptor expression when compared to C., Fibroblasts are the major mesenchymal cells present within the interstitium of the lung and have been shown to be a major source of VEGF [4]. VEGF in the lung is required to maintain endothelial cell survival of pulmonary capillaries and therefore a normal alveolar wall [28], but VEGF is also an extremely potent pro-angiogenic factor, 13 and relatively small changes in its concentrations may promote pathological blood vessel expansion.…”

Angiotensin II in apoptotic lung injury: potential role in meconium aspiration syndrome

“…One example is vascular endothelial growth factor (VGEF); decreased VGEF expression or blockade of VGEF receptors caused emphysematous changes in lung architecture. 29,30 Another group of endogenous mediators believed to play role in apoptosis of parenchymal cells of the lung in COPD is TNF-a, FasL and Fas. However, it is unclear at present whether these molecules are elevated or contribute to the severity of COPD [31][32][33] and more work is needed to clarify these issues.…”