scholarly journals Role of ROS in ischemia-induced lung angiogenesis

2010 ◽  
Vol 299 (4) ◽  
pp. L535-L541 ◽  
Author(s):  
Julie Nijmeh ◽  
Aigul Moldobaeva ◽  
Elizabeth M. Wagner
Keyword(s):  
Pulmonary Artery ◽  
Left Lung ◽  
Left Pulmonary Artery ◽  
Wild Type ◽  
Systemic Blood Flow ◽  
Artery Ligation ◽  
Underlying Mechanisms ◽  
Pulmonary Artery Obstruction ◽  
Artery Obstruction

Pulmonary artery obstruction and subsequent lung ischemia have been shown to induce systemic angiogenesis despite preservation of normoxia. The underlying mechanisms, however, remain poorly understood. In a mouse model of lung ischemia induced by left pulmonary artery ligation (LPAL), we showed previously, the formation of a new systemic vasculature to the ischemic lung. We hypothesize that LPAL in the mouse increases reactive oxygen species (ROS) production, and these molecules play an initiating role in subsequent lung neovascularization. We used oxidant-sensitive dyes (DHE and H2DCF-DA) to quantify ROS and measured the antioxidant-reduced glutathione (GSH) and its oxidized form (GSSG) as indicators of ROS levels after LPAL. The magnitude of systemic neovascularization was determined by measuring systemic blood flow to the left lung with radiolabeled microspheres 14 days after LPAL. An increase in ROS was observed early (30 min: 55% increase in H2DCF-DA) after LPAL, with a return to baseline by 24 h. GSH/GSSG was decreased (∼50%) 4 h after LPAL, suggesting earlier ROS upregulation. Mice treated with the antioxidant N-acetylcysteine showed attenuated angiogenesis (62% of wild-type LPAL), and mice lacking Nrf2, a transcription factor important for antioxidant synthesis, resulted in increased neovascularization (207% of wild-type LPAL). Overall, GSH/GSSG was inversely associated with the magnitude of neovascularization. These results demonstrate that LPAL induces an early and transient ROS upregulation, and ROS appear to play a role in promoting ischemia-induced angiogenesis.

scholarly journals The role of CXCR2 in systemic neovascularization of the mouse lung

2007 ◽  
Vol 103 (2) ◽  
pp. 594-599 ◽  
Author(s):  
Jesús Sánchez ◽  
Aigul Moldobaeva ◽  
Jessica McClintock ◽  
John Jenkins ◽  
Elizabeth Wagner
Keyword(s):  
Blood Flow ◽  
Pulmonary Artery ◽  
Left Lung ◽  
Neutralizing Antibody ◽  
Left Pulmonary Artery ◽  
Endothelial Cell Proliferation ◽  
Antibody Treatment ◽  
Pulmonary Artery Obstruction ◽  
Artery Obstruction ◽  
Deficient Mice

We previously showed increased expression of the ELR+, CXC chemokines in the lung after left pulmonary artery obstruction. These chemokines have been shown in other systems to bind their G protein-coupled receptor, CXCR2, and promote systemic endothelial cell proliferation, migration, and capillary tube formation. In the present study, we blocked CXCR2 in vivo using a neutralizing antibody and also studied mice that were homozygous null for CXCR2. To estimate the extent of neovascularization in this model, we measured systemic blood flow to the left lung 14 days after left pulmonary artery ligation (LPAL). We found blood flow significantly reduced (67% decrease) with neutralizing antibody treatment compared with controls. However, blood flow was not altered in the CXCR2-deficient mice compared with wild-type controls after LPAL. To test for ligand availability, we measured macrophage inflammatory protein (MIP)-2 in lung homogenates after LPAL, because this is the predominant CXC chemokine previously shown to be increased after LPAL ( 22 ). MIP-2 protein was two- to fourfold higher in the left lung relative to the right lung in all treatment groups 4 h after LPAL and this increase did not differ among groups. We speculate that the CXCR2-deficient mice have compensatory mechanisms that mitigate their lack of gene expression and conclude that CXCR2 contributes to chemokine-induced systemic angiogenesis after pulmonary artery obstruction.

scholarly journals Changes in lung permeability after chronic pulmonary artery obstruction

2006 ◽  
Vol 100 (4) ◽  
pp. 1224-1229 ◽  
Author(s):  
Elizabeth M. Wagner ◽  
Gulnura Karagulova ◽  
John Jenkins ◽  
John Bishai ◽  
Jessica McClintock
Keyword(s):  
Pulmonary Artery ◽  
Evans Blue ◽  
Left Lung ◽  
Weight Ratio ◽  
Dry Weight ◽  
Blue Dye ◽  
Artery Ligation ◽  
Wet Weight ◽  
Pulmonary Artery Obstruction ◽  
Artery Obstruction

We have shown that left pulmonary artery ligation (LPAL) in mice causes a prompt angiogenic response, with new systemic vessels from intercostal arteries penetrating the pleura within 6 days. Because angiogenic vessels in other organs have been shown to exhibit increased permeability, we studied vascular permeability (Evans blue dye extravasation, lung wet weight-to-dry weight ratio, and lavaged protein) in naive C57BL/6 mice and 4 h, and 14 and 21 days after LPAL (4–6 mice/time point). We also measured radiolabel clearance as an index of functional perfusion after LPAL. Tracer clearance from the left lung was maximal by 6 days after LPAL and not different from right lungs. Thus a functional vasculature is established before 6 days of LPAL that results in normal tracer clearance. By 21 days after LPAL, Evans blue-albumin was significantly increased in the left lung relative to both 4 h (no vasculature) and 14 days after LPAL. Only after 21 days of LPAL was left lung wet weight-to-dry weight ratio significantly different from naive lungs. Additionally, lavaged protein was significantly increased both 4 h and 21 days after LPAL relative to control mice. Thus, using three different methods, results consistently demonstrated increased permeability to protein and water 21 days after LPAL. Although changes in surface area of perfusion might affect the interpretation of these results, blood flow measured with labeled microspheres indicated no change in left lung perfusion between 14 and 21 days of LPAL. Thus the lung vasculature, remodeled as a consequence of chronic pulmonary artery obstruction, demonstrates increased water and protein permeability.

Unintended Pulmonary Artery Ligation during PDA Ligation

2016 ◽  
Vol 19 (4) ◽  
pp. 187 ◽  
Author(s):  
Dohun Kim ◽  
Si-Wook Kim ◽  
Hong-Ju Shin ◽  
Jong-Myeon Hong ◽  
Ji Hyuk Lee ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Ductus Arteriosus ◽  
Left Lung ◽  
Left Pulmonary Artery ◽  
Chest Ct ◽  
Mechanical Ventilator ◽  
Artery Ligation ◽  
Ventilator Support ◽  
Surgical Ligation ◽  
Emergent Operation

A 10-day-old boy was transferred to our hospital due to tachypnea. Patent ductus arteriosus (PDA), 4.8 mm in diameter, with small ASD was diagnosed on echocardiography. Surgical ligation of the ductus was performed after failure of three cycles of ibuprofen. However, the ductus remained open on routine postoperative echocardiography on the second postoperative day, and chest CT revealed inadvertent ligation of the left pulmonary artery (LPA) rather than the PDA. Emergent operation successfully reopened the clipped LPA and ligated the ductus on the same (second postoperative) day.<br />Mechanical ventilator support was weaned on postoperative day 21, and the baby was discharged on postoperative day 47 with a normal left lung shadow.

Giant Left Atrium as Cause of Left Pulmonary Artery Obstruction

1987 ◽  
Vol 43 (3) ◽  
pp. 329-331 ◽  
Author(s):  
A. Jorge S. Serra ◽  
Kathleen W. McNicholas ◽  
Gerald M. Lemole
Keyword(s):  
Pulmonary Artery ◽  
Left Atrium ◽  
Left Pulmonary Artery ◽  
Giant Left Atrium ◽  
Pulmonary Artery Obstruction ◽  
Artery Obstruction

Adult Case of Ductus arteriosus Aneurysm Complicated with Left Pulmonary Artery Obstruction

1994 ◽  
Vol 8 (2) ◽  
pp. 109-111
Author(s):  
Yasushi Sunaga ◽  
Kayo Hayashi ◽  
Tetsuro Sugiura ◽  
Nobuyuki Tsuda ◽  
Torn Seki ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Ductus Arteriosus ◽  
Left Pulmonary Artery ◽  
Adult Case ◽  
Ductus Arteriosus Aneurysm ◽  
Pulmonary Artery Obstruction ◽  
Artery Obstruction

Large and Medium-Sized Pulmonary Artery Obstruction Does Not Play a Role of Primary Importance in the Etiology of Sickle-Cell Disease-Associated Pulmonary Hypertension

CHEST Journal ◽  
2008 ◽  
Vol 133 (3) ◽  
pp. 646-652 ◽  
Author(s):  
Eduard J. van Beers ◽  
Berthe L.F. van Eck-Smit ◽  
Melvin R. Mac Gillavry ◽  
Charlotte F.J. van Tuijn ◽  
Joost W.J. van Esser ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Sickle Cell Disease ◽  
Pulmonary Artery ◽  
Sickle Cell ◽  
Cell Disease ◽  
Pulmonary Artery Obstruction ◽  
Artery Obstruction

scholarly journals Role of IL-6 in systemic angiogenesis of the lung

2005 ◽  
Vol 99 (3) ◽  
pp. 861-866 ◽  
Author(s):  
Jessica Y. McClintock ◽  
Elizabeth M. Wagner
Keyword(s):  
Cardiac Output ◽  
Left Lung ◽  
Fold Increase ◽  
Left Pulmonary Artery ◽  
Artery Ligation ◽  
Vessel Growth ◽  
Pulmonary Ischemia ◽  
Cell Profile ◽  
Multifunctional Cytokine

The multifunctional cytokine interleukin (IL)-6 has been shown to modulate inflammation and angiogenesis. In a mouse model of lung angiogenesis induced by chronic left pulmonary artery ligation (LPAL), we previously showed increased expression of IL-6 mRNA in lung homogenates 4 h after the onset of pulmonary ischemia ( 31 ). To determine whether IL-6 influences both new vessel growth and inflammatory cell influx, we studied wild-type (WT) and IL-6-deficient C57Bl/6J (KO) mice after LPAL (4 h and 1, 7, 14 days). We measured IL-6 protein of the lung by ELISA, the lavage cell profile of the left lung, and new systemic vessel growth with radiolabeled microspheres (14 days after LPAL) in WT and KO mice. We confirmed a 2.4-fold increase in IL-6 protein in the left lung of WT mice compared with right lung 4 h after LPAL. A significant increase in lavaged neutrophils (7.5% of total cells) was observed only in WT mice 4 h after LPAL. New vessel growth was significantly attenuated in KO relative to WT (0.7 vs. 1.9% cardiac output). In an additional series, treatment of WT mice with anti-neutrophil antibody demonstrated a reduction in lavaged neutrophils 4 h after LPAL; however, IL-6 protein remained elevated and neovascularization to the left lung (2.3% cardiac output) was not altered. These results demonstrate that IL-6 plays an important modulatory role in lung angiogenesis, but the changes are not dependent on trapped neutrophils.

scholarly journals Lung and vascular function during chronic severe pulmonary ischemia

2011 ◽  
Vol 110 (2) ◽  
pp. 538-544 ◽  
Author(s):  
Elizabeth M. Wagner ◽  
John Jenkins ◽  
Maria Grazia Perino ◽  
Adlah Sukkar ◽  
Wayne Mitzner
Keyword(s):  
Pulmonary Artery ◽  
Vascular Permeability ◽  
Lung Tissue ◽  
Lung Volume ◽  
Left Lung ◽  
Left Pulmonary Artery ◽  
Lung Pathology ◽  
Diffusing Capacity ◽  
Artery Ligation ◽  
Pulmonary Ischemia

Bronchial vascular angiogenesis takes place in a variety of lung inflammatory conditions such as asthma, cystic fibrosis, lung cancer, and chronic pulmonary thromboembolic disease. However, it is unclear whether neovascularization is predominantly appropriate and preserves lung tissue or whether it contributes further to lung pathology through edema formation and inflammation. In the present study we examined airway and lung parenchymal function 14 days after left pulmonary artery ligation. In rats as well as higher mammals, severe pulmonary ischemia results in bronchial vascular proliferation. Using labeled microspheres, we demonstrated an 18-fold increase in systemic blood flow to the ischemic left lung. Additionally, vascular remodeling extended to the tracheal venules, which showed an average 28% increase in venular diameter. Despite this increase in vascularity, airways resistance was not altered nor was methacholine responsiveness. Since these measurements include the entire lung, we suggest that the normal right lung, which represented 78% of the total lung, obscured the ability to detect a change. When functional indexes such as diffusing capacity, in situ lung volume, and vascular permeability of the left lung could be separated from right lung, significant changes were observed. Thus when comparing average left lung values of rats 14 days after left pulmonary artery ligation to left lungs of rats undergoing sham surgery, diffusing capacity of the left lung decreased by 72%, left lung volume decreased by 38%, and the vascular permeability to protein increased by 58%. No significant differences in inflammatory cell recruitment were observed, suggesting that acute ischemic inflammation had resolved. We conclude that despite the preservation of lung tissue, the proliferating bronchial neovasculature may contribute to a sustained decrement in pulmonary function.

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