Limits...
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.

Show MeSH

Related in: MedlinePlus

Corrosion casts of new alveolar septum formation. a In the midline of the alveolar cavity, an elevated vessel (dotted red line) starts to upfold, whereby another double-layered vessel crosses under it. b The septal vessel continues to elevate tightened dumbbell-shaped by two vessel at the end (white arrows). c A septal ridge (red dotted line) can be seen in the middle of the alveolar cavity whose local influxes (white arrows) are increasing by pillar formation (yellow stars) and vascular duplications. d Upfolding of a new alveolar septum (red dotted line) starts towards the alveolar entrance ring (AER). A second double-layered ring (orange dotted line) is developing by intussusceptive angiogenesis (yellow stars). e In the developed new alveoli with AERs (red dotted lines), an elevation and formation of new septa (red lines) is present in the midline. f Vascular remodeling modifies and expands the alveolar basket by the occurrence of pillars, typical hallmarks of intussusceptive angiogenesis (circle)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4061467&req=5

Fig5: Corrosion casts of new alveolar septum formation. a In the midline of the alveolar cavity, an elevated vessel (dotted red line) starts to upfold, whereby another double-layered vessel crosses under it. b The septal vessel continues to elevate tightened dumbbell-shaped by two vessel at the end (white arrows). c A septal ridge (red dotted line) can be seen in the middle of the alveolar cavity whose local influxes (white arrows) are increasing by pillar formation (yellow stars) and vascular duplications. d Upfolding of a new alveolar septum (red dotted line) starts towards the alveolar entrance ring (AER). A second double-layered ring (orange dotted line) is developing by intussusceptive angiogenesis (yellow stars). e In the developed new alveoli with AERs (red dotted lines), an elevation and formation of new septa (red lines) is present in the midline. f Vascular remodeling modifies and expands the alveolar basket by the occurrence of pillars, typical hallmarks of intussusceptive angiogenesis (circle)

Mentions: The assessment of microvascular corrosion casts detected the evidence of new alveolar septum formation by alveolar duplication and capillary remodeling in compensatory lung growth after pneumonectomy. SEM- and high resolution SRXTM images of microvascular casts revealed in early stages of new alveolus formation an elevated vessel in the midline of alveolar cavity crossed by an underlaying vessel (Fig. 5a). The maturation of these alveolar septa continues by lifting off of this ridge-like vessel that is dumbbell-shaped connected to the perialveolar plexus vessels on both sides (Fig. 5b). The elevation of the ridge is accompagnied by the occurrence of intussusceptive angiogenesis ensuring a rapid expansion of the alveolar microvascular network and vascular duplications of the septal vessels (Fig. 5c). A second double-layered ring can be observed at the point when upfolding of the new alveolar septum reaches the same level as the alveolar entrance ring (AER) (Fig. 5d). In the completely developed alveoli, an elevated formation of new septa is evident in the midline (Fig. 5e). Maturation of alveolar vascular network is then modified and finished by the appearance of vascular remodeling and intussusceptive angiogenesis (Fig. 5f). A tomographic analysis of microvascular corrosion casts acquired by synchtron-radiation confirmed these observations (Fig. 6).Fig. 5


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)

Corrosion casts of new alveolar septum formation. a In the midline of the alveolar cavity, an elevated vessel (dotted red line) starts to upfold, whereby another double-layered vessel crosses under it. b The septal vessel continues to elevate tightened dumbbell-shaped by two vessel at the end (white arrows). c A septal ridge (red dotted line) can be seen in the middle of the alveolar cavity whose local influxes (white arrows) are increasing by pillar formation (yellow stars) and vascular duplications. d Upfolding of a new alveolar septum (red dotted line) starts towards the alveolar entrance ring (AER). A second double-layered ring (orange dotted line) is developing by intussusceptive angiogenesis (yellow stars). e In the developed new alveoli with AERs (red dotted lines), an elevation and formation of new septa (red lines) is present in the midline. f Vascular remodeling modifies and expands the alveolar basket by the occurrence of pillars, typical hallmarks of intussusceptive angiogenesis (circle)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4061467&req=5

Fig5: Corrosion casts of new alveolar septum formation. a In the midline of the alveolar cavity, an elevated vessel (dotted red line) starts to upfold, whereby another double-layered vessel crosses under it. b The septal vessel continues to elevate tightened dumbbell-shaped by two vessel at the end (white arrows). c A septal ridge (red dotted line) can be seen in the middle of the alveolar cavity whose local influxes (white arrows) are increasing by pillar formation (yellow stars) and vascular duplications. d Upfolding of a new alveolar septum (red dotted line) starts towards the alveolar entrance ring (AER). A second double-layered ring (orange dotted line) is developing by intussusceptive angiogenesis (yellow stars). e In the developed new alveoli with AERs (red dotted lines), an elevation and formation of new septa (red lines) is present in the midline. f Vascular remodeling modifies and expands the alveolar basket by the occurrence of pillars, typical hallmarks of intussusceptive angiogenesis (circle)
Mentions: The assessment of microvascular corrosion casts detected the evidence of new alveolar septum formation by alveolar duplication and capillary remodeling in compensatory lung growth after pneumonectomy. SEM- and high resolution SRXTM images of microvascular casts revealed in early stages of new alveolus formation an elevated vessel in the midline of alveolar cavity crossed by an underlaying vessel (Fig. 5a). The maturation of these alveolar septa continues by lifting off of this ridge-like vessel that is dumbbell-shaped connected to the perialveolar plexus vessels on both sides (Fig. 5b). The elevation of the ridge is accompagnied by the occurrence of intussusceptive angiogenesis ensuring a rapid expansion of the alveolar microvascular network and vascular duplications of the septal vessels (Fig. 5c). A second double-layered ring can be observed at the point when upfolding of the new alveolar septum reaches the same level as the alveolar entrance ring (AER) (Fig. 5d). In the completely developed alveoli, an elevated formation of new septa is evident in the midline (Fig. 5e). Maturation of alveolar vascular network is then modified and finished by the appearance of vascular remodeling and intussusceptive angiogenesis (Fig. 5f). A tomographic analysis of microvascular corrosion casts acquired by synchtron-radiation confirmed these observations (Fig. 6).Fig. 5

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