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Sprouting and intussusceptive angiogenesis in postpneumonectomy lung growth: mechanisms of alveolar neovascularization.

Ackermann M, Houdek JP, Gibney BC, Ysasi A, Wagner W, Belle J, Schittny JC, Enzmann F, Tsuda A, Mentzer SJ, Konerding MA - Angiogenesis (2013)

Bottom Line: 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.In addition, the appearance of pillar formations and duplications on alveolar entrance ring vessels in mature alveoli are indicative of vascular remodeling.Various forms of developmental neoalveolarization may also be considered to contribute in compensatory lung regeneration.

View Article: PubMed Central - PubMed

Affiliation: Institute of Functional and Clinical Anatomy, University Medical Center of the Johannes Gutenberg-University Mainz, 55128, Mainz, Germany.

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.

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Sprouting and intussusceptive angiogenesis on pleural plexus. The pleural surface of the cardiac lobe is underlaid by a highly ramified capillary plexus originating from and draining to pulmonary vessel branches. a Coverage of approximately 15–25 % of the pleural surface. Bar = 50 μm. b 7 days after pneumonectomy this plexus increases in density, focally resulting in coverage of up to 85 %. Bar = 50 μm. c Numerous small caliber holes with diameters of between 1 and 5 μm as hallmarks of pillar formation (white arrows) show the high intussusceptive angiogenesis activity. Bar = 25 μm. d In less densely packed areas sprouts (red arrowheads) as well as pillars are evident. Bar = 20 μm
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Fig3: Sprouting and intussusceptive angiogenesis on pleural plexus. The pleural surface of the cardiac lobe is underlaid by a highly ramified capillary plexus originating from and draining to pulmonary vessel branches. a Coverage of approximately 15–25 % of the pleural surface. Bar = 50 μm. b 7 days after pneumonectomy this plexus increases in density, focally resulting in coverage of up to 85 %. Bar = 50 μm. c Numerous small caliber holes with diameters of between 1 and 5 μm as hallmarks of pillar formation (white arrows) show the high intussusceptive angiogenesis activity. Bar = 25 μm. d In less densely packed areas sprouts (red arrowheads) as well as pillars are evident. Bar = 20 μm

Mentions: The spatially heterogeneous compensatory lung growth is mainly driven by two different forms of angiogenesis: sprouting and non-sprouting (intussusceptive) angiogenesis. In the subpleural vascular plexus both forms are involved (Fig. 3). High resolution synchrotron radiation tomography revealed in growth zones around the major vessels predominantly intussusceptive pillars (Fig. 6c). The expansion of the pleural vascular plexus is carried out principally by the vasodilation and the incidence of intussusceptive pillars. In addition to our SEM-results, this finding was confirmed by the occurrence of transcapillary pillar formation in transelectron microsopy (Fig. 4a). The rapid expansion of central vascular network is paralleled by an extensive recruitment of pro-angiogenic cells as alveolar macrophages and pneumocytes type II. A subcellular analysis of alveolar cell structure revealed a close spatial relationship between pneumocytes type II and alveolar macrophages participating in alveolar morphogenesis of post-pneumonectomy lung growth (Fig. 4b–d).Fig. 3


Sprouting and intussusceptive angiogenesis in postpneumonectomy lung growth: mechanisms of alveolar neovascularization.

Ackermann M, Houdek JP, Gibney BC, Ysasi A, Wagner W, Belle J, Schittny JC, Enzmann F, Tsuda A, Mentzer SJ, Konerding MA - Angiogenesis (2013)

Sprouting and intussusceptive angiogenesis on pleural plexus. The pleural surface of the cardiac lobe is underlaid by a highly ramified capillary plexus originating from and draining to pulmonary vessel branches. a Coverage of approximately 15–25 % of the pleural surface. Bar = 50 μm. b 7 days after pneumonectomy this plexus increases in density, focally resulting in coverage of up to 85 %. Bar = 50 μm. c Numerous small caliber holes with diameters of between 1 and 5 μm as hallmarks of pillar formation (white arrows) show the high intussusceptive angiogenesis activity. Bar = 25 μm. d In less densely packed areas sprouts (red arrowheads) as well as pillars are evident. Bar = 20 μm
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4061467&req=5

Fig3: Sprouting and intussusceptive angiogenesis on pleural plexus. The pleural surface of the cardiac lobe is underlaid by a highly ramified capillary plexus originating from and draining to pulmonary vessel branches. a Coverage of approximately 15–25 % of the pleural surface. Bar = 50 μm. b 7 days after pneumonectomy this plexus increases in density, focally resulting in coverage of up to 85 %. Bar = 50 μm. c Numerous small caliber holes with diameters of between 1 and 5 μm as hallmarks of pillar formation (white arrows) show the high intussusceptive angiogenesis activity. Bar = 25 μm. d In less densely packed areas sprouts (red arrowheads) as well as pillars are evident. Bar = 20 μm
Mentions: The spatially heterogeneous compensatory lung growth is mainly driven by two different forms of angiogenesis: sprouting and non-sprouting (intussusceptive) angiogenesis. In the subpleural vascular plexus both forms are involved (Fig. 3). High resolution synchrotron radiation tomography revealed in growth zones around the major vessels predominantly intussusceptive pillars (Fig. 6c). The expansion of the pleural vascular plexus is carried out principally by the vasodilation and the incidence of intussusceptive pillars. In addition to our SEM-results, this finding was confirmed by the occurrence of transcapillary pillar formation in transelectron microsopy (Fig. 4a). The rapid expansion of central vascular network is paralleled by an extensive recruitment of pro-angiogenic cells as alveolar macrophages and pneumocytes type II. A subcellular analysis of alveolar cell structure revealed a close spatial relationship between pneumocytes type II and alveolar macrophages participating in alveolar morphogenesis of post-pneumonectomy lung growth (Fig. 4b–d).Fig. 3

Bottom Line: 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.In addition, the appearance of pillar formations and duplications on alveolar entrance ring vessels in mature alveoli are indicative of vascular remodeling.Various forms of developmental neoalveolarization may also be considered to contribute in compensatory lung regeneration.

View Article: PubMed Central - PubMed

Affiliation: Institute of Functional and Clinical Anatomy, University Medical Center of the Johannes Gutenberg-University Mainz, 55128, Mainz, Germany.

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.

Show MeSH
Related in: MedlinePlus