, Volume 15, Issue 1, pp 23–32 | Cite as

Spatial dependence of alveolar angiogenesis in post-pneumonectomy lung growth

  • Moritz A. Konerding
  • Barry C. Gibney
  • Jan P. Houdek
  • Kenji Chamoto
  • Maximilian Ackermann
  • Grace S. Lee
  • Miao Lin
  • Akira Tsuda
  • Steven J. Mentzer
Original Paper


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.


Scanning electron microscopy Corrosion casting Neoalveolarization Intussusceptive angiogenesis MicroCT 







Cardiac lobe




Lung weight index


Mean linear intercept


Phosphate buffered saline


Right lower lobe


Right middle lobe


Right upper lobe


Standard deviation


Scanning electron microscopy


Total body weight



This work was supported by NIH grants HL75426, HL94567 and HL007734 as well as the Uehara Memorial Foundation and the JSPS Postdoctoral Fellowships for Research Abroad.


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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Moritz A. Konerding
    • 1
  • Barry C. Gibney
    • 2
  • Jan P. Houdek
    • 1
  • Kenji Chamoto
    • 2
  • Maximilian Ackermann
    • 1
  • Grace S. Lee
    • 2
  • Miao Lin
    • 2
  • Akira Tsuda
    • 3
  • Steven J. Mentzer
    • 2
  1. 1.Institute of Functional and Clinical AnatomyUniversity Medical Center of Johannes Gutenberg-UniversityMainzGermany
  2. 2.Laboratory of Adaptive and Regenerative BiologyBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA
  3. 3.Molecular and Integrative Physiological SciencesHarvard School of Public HealthBostonUSA

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