Increased distension stimulates distal capillary growth as well as expression of specific angiogenesis genes in fetal mouse lungs

Tracheal occlusion (TO) performed surgically in utero near the end of gestation causes a rapid increase in the distension of future airspaces, resulting in accelerated lung development. The authors hypothesize that TO stimulates microvascular growth concomitant with a rapid increase in the expression of genes implicated in angiogenesis. Mouse fetuses underwent in utero surgery (TO or sham-TO surgery) at 16.5 days of gestation, whereupon development was allowed to continue for a further 1 or 24 hours. Microvascular changes were assessed by immunohistochemical staining of fetal lung sections for platelet endothelial cell adhesion molecule-1. Levels of vascular endothelial growth factor-A (VEGF-A; isoforms 120, 164 and 188), VEGF receptors 1 and 2 (VEGFR-1 and -2), angiopoietins 1 and 2, and Tie2 mRNAs were determined by quantitative real-time polymerase chain reaction (PCR). The authors observed more intercapillary interconnection, less isolated capillaries, and a more extended capillary network inside septa of lungs that underwent 24 h of TO versus sham-TO. Moreover, the authors observed a significant increase in mRNA levels of VEGF 188 and VEGFR-1 as early as 1 hour following TO and of VEGFR-1 and angiopoietin 1 after 24 hours. Together, these results suggest that surgically applied stretching quickly enhances the expression of specific angiogenesis and vessel maintenance genes, which seems to result in the maturation and organization of a more extensive and complex capillary network.