title: Spatial dependence of alveolar angiogenesis in post-pneumonectomy lung growth.
abstract: Growth of the remaining lung after pneumonectomy has been observed in many mammalian species; nonetheless, the pattern and morphology of alveolar angiogenesis during compensatory growth is unknown. Here, we investigated alveolar angiogenesis in a murine model of post-pneumonectomy lung growth. As expected, the volume and weight of the remaining lung returned to near-baseline levels within 21 days of pneumonectomy. The percentage increase in lobar weight was greatest in the cardiac lobe (P < 0.001). Cell cycle flow cytometry demonstrated a peak of lung cell proliferation (12.02 ± 1.48%) 6 days after pneumonectomy. Spatial autocorrelation analysis of the cardiac lobe demonstrated clustering of similar vascular densities (positive autocorrelation) that consistently mapped to subpleural regions of the cardiac lobe. Immunohistochemical staining demonstrated increased cell density and enhanced expression of angiogenesis-related factors VEGFA, and GLUT1 in these subpleural regions. Corrosion casting and scanning electron microscopy 3-6 days after pneumonectomy demonstrated subpleural vessels with angiogenic sprouts. The monopodial sprouts appeared to be randomly oriented along the vessel axis with interbranch distances of 11.4 ± 4.8 μm in the regions of active angiogenesis. Also present within the regions of increased vascular density were frequent "holes" or "pillars" consistent with active intussusceptive angiogenesis. The mean pillar diameter was 4.2 ± 3.8 μm, and the pillars were observed in all regions of active angiogenesis. These findings indicate that the process of alveolar construction involves discrete regions of regenerative growth, particularly in the subpleural regions of the cardiac lobe, characterized by both sprouting and intussusceptive angiogenesis.
authors.affiliation: Institute of Functional and Clinical Anatomy, University Medical Center of Johannes Gutenberg-University, Mainz, Germany.
authors.forename: Moritz A
authors.initials: MA
authors.lastname: Konerding
authors.forename: Barry C
authors.initials: BC
authors.lastname: Gibney
authors.forename: Jan P
authors.initials: JP
authors.lastname: Houdek
authors.forename: Kenji
authors.initials: K
authors.lastname: Chamoto
authors.forename: Maximilian
authors.initials: M
authors.lastname: Ackermann
authors.forename: Grace S
authors.initials: GS
authors.lastname: Lee
authors.forename: Miao
authors.initials: M
authors.lastname: Lin
authors.forename: Akira
authors.initials: A
authors.lastname: Tsuda
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Mentzer
mesh_terms: D000818:Animals; D002453:Cell Cycle; D005434:Flow Cytometry; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic; D009929:Organ Size; D010994:Pleura / Q000473:pathology; D011013:Pneumonectomy; D011650:Pulmonary Alveoli / Q000098:blood supply* / Q000254:growth & development* / Q000473:pathology / Q000648:ultrastructure; D013997:Time Factors