Abstract
In most rodents and some other mammals, the removal of one lung results in compensatory growth associated with dramatic angiogenesis and complete restoration of lung capacity. One pivotal mechanism in neoalveolarization is neovascularization, because without angiogenesis new alveoli can not be formed. The aim of this study is to image and analyze three-dimensionally the different patterns of neovascularization seen following pneumonectomy in mice on a sub-micron-scale. C57/BL6 mice underwent a left-sided pneumonectomy. Lungs were harvested at various timepoints after pneumonectomy. Volume analysis by microCT revealed a striking increase of 143 percent in the cardiac lobe 14 days after pneumonectomy. Analysis of microvascular corrosion casting demonstrated spatially heterogenous vascular densitities which were in line with the perivascular and subpleural compensatory growth pattern observed in anti-PCNA-stained lung sections. Within these regions an expansion of the vascular plexus with increased pillar formations and sprouting angiogenesis, originating both from pre-existing bronchial and pulmonary vessels was observed. Also, type II pneumocytes and alveolar macrophages were seen to participate actively in alveolar neo-angiogenesis after pneumonectomy. 3D-visualizations obtained by high-resolution synchrotron radiation X-ray tomographic microscopy showed the appearance of double-layered vessels and bud-like alveolar baskets as have already been described in normal lung development. Scanning electron microscopy data of microvascular architecture also revealed a replication of perialveolar vessel networks through septum formation as already seen in developmental alveolarization. In addition, the appearance of pillar formations and duplications on alveolar entrance ring vessels in mature alveoli are indicative of vascular remodeling. These findings indicate that sprouting and intussusceptive angiogenesis are pivotal mechanisms in adult lung alveolarization after pneumonectomy. Various forms of developmental neoalveolarization may also be considered to contribute in compensatory lung regeneration.Electronic supplementary materialThe online version of this article (doi:10.1007/s10456-013-9399-9) contains supplementary material, which is available to authorized users.
Highlights
In 2010, more than 50 million individuals worldwide were suffering from life-threatening end-stage lung diseases in the US alone, with 240.000 patients undergoing lung surgery [1, 2]
MicroCT measurements of different volumes of thr cardiac lobe after pneumonectomy showed a steep augmentation of 143 % on day 14 as a result of the high increase in proliferation that peaks on day six after pneumonectomy as detailed in our previous work
The present study looked at the morphogenetic evidence of angiogenesis in compensatory lung growth after pneumonectomy
Summary
In 2010, more than 50 million individuals worldwide were suffering from life-threatening end-stage lung diseases in the US alone, with 240.000 patients undergoing lung surgery [1, 2]. Pneumonectomy in small laboratory animals results in compensatory lung growth with complete restoration of the lung capacity [3]. Recent evidence suggests that compensatory growth may occur—but the time course is months to years rather than days to weeks [4]. One key element of this regenerative process is lung angiogenesis during the formation of new alveoli. New blood vessel formation after pneumonectomy shows many parallels to angiogenesis during normal lung development [5]. Between birth and adolescence in lung development, a 23-fold increase in the lung volume becomes apparent. Lung microvasculature grows even more: capillary volume increases by a factor of 35. The development of the alveolar capillary meshwork is a complex morphogenetic process requiring blood vessel and alveolus construction, and the efficient matching of ventilation and blood flow
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call