Increased lung matrix metalloproteinase-9 levels in extremely premature baboons with bronchopulmonary dysplasia

Tambunting, F.; Beharry, Kay D.; Hartleroad, J. Y.; Waltzman, Joshua; Stavitsky, Yuri; Modanlou, Houchang D.

doi:10.1002/ppul.20135

Cited by 47 publications

(45 citation statements)

References 34 publications

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“…Similarly, MV in preterm baboons reduces collagen expression and increases the expression of matrix metalloproteinase 9, which is known to break down type I collagen (45). However, it is also possible that the decreased relative collagen and elastin abundances we observed were due to the increase in tissue space, rather than loss of ECM.…”

Section: Discussioncontrasting

confidence: 46%

Injury and repair in the very immature lung following brief mechanical ventilation

Brew¹,

Hooper

Allison

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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Mechanical ventilation (MV) of very premature infants contributes to lung injury and bronchopulmonary dysplasia (BPD), the effects of which can be long-lasting. Little is currently known about the ability of the very immature lung to recover from ventilator-induced lung injury. Our objective was to determine the ability of the injured very immature lung to repair in the absence of continued ventilation and to identify potential mechanisms. At 125 days gestational age (days GA, 0.85 of term), fetal sheep were partially exposed by hysterotomy under anesthesia and aseptic conditions; they were intubated and ventilated for 2 h with an injurious MV protocol and then returned to the uterus to continue development. Necropsy was performed at either 1 day (short-term group, 126 days GA, n ϭ 6) or 15 days (long-term group, 140 days GA, n ϭ 5) after MV; controls were unventilated (n ϭ 7-8). At 1 day after MV, lungs displayed signs of injury, including hemorrhage, disorganized elastin and collagen deposition in the distal airspaces, altered morphology, significantly reduced secondary septal crest density, and decreased airspace. Bronchioles had thickened epithelium with evidence of injury and sloughing. Relative mRNA levels of early response genes (connective tissue growth factor, cysteine-rich 61, and early growth response-1) and proinflammatory cytokines [interleukins (IL)-1␤, IL-6, IL-8, tumor necrosis factor-␣, and transforming growth factor-␤] were not different between groups 1 day after MV. At 15 days after MV, lung structure was normal with no evidence of injury. We conclude that 2 h of MV induces severe injury in the very immature lung and that these lungs have the capacity to repair spontaneously in the absence of further ventilation.ventilator induced lung injury; bronchopulmonary dysplasia; repair; inflammation; preterm birth VERY PRETERM INFANTS OFTEN require mechanical ventilation (MV) due to respiratory insufficiency. However, respiratory support including MV can injure the immature lung and contribute to the development of bronchopulmonary dysplasia (BPD) (10). Structural changes in the lung that are associated with MV and BPD can persist, resulting in deficits in lung function in children (17,19) and young adults (18). Consistent with this, exercise capacity is reduced in children (23, 32) and adolescents (31, 33) who were born very preterm and developed BPD. The structural changes seen in the lungs of infants with BPD include hypercellularity, fewer and larger alveoli, altered vascular growth, and disorganized elastin and collagen deposition (12). In addition, alterations to the small conducting airways have been reported in BPD-affected infants, including increases in airway smooth muscle and the number of goblet cells (47).The causes of BPD remain unclear. While MV is known to be a significant contributor to BPD, other factors are thought to be involved, including infection, use of supplemental oxygen, and impaired nutrition (27). Indeed it has been difficult to identify the role of MV alone, or any othe...

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Section: Discussioncontrasting

confidence: 46%

Injury and repair in the very immature lung following brief mechanical ventilation

Brew¹,

Hooper

Allison

et al. 2011

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Elevated levels of the other gelatinase, MMP9, and high MMP9/TIMP1 ratio rather appear to be associated with the later, regenerative and chronic phases of the disease, and with fibrosis (48,49). A similar pattern was found in the extremely premature ventilated baboon (50).…”

Section: Other Ecm Components Ecm Remodeling and Interactions With supporting

confidence: 55%

Control Mechanisms of Lung Alveolar Development and Their Disorders in Bronchopulmonary Dysplasia

et al. 2005

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“…Increased MMP-9 activity after hyperoxia has been linked to later BPD development (30). There is also an increasing body of research showing that MMPs, and specifically MMP-2 and MMP-9, are involved in tumor growth and metastasis and may have a role in acute lymphoblastic leukemia (ALL) (31,32).…”

Section: Discussionmentioning

confidence: 99%

Resuscitation of Hypoxic Newborn Piglets With Supplementary Oxygen Induces Dose-Dependent Increase in Matrix Metalloproteinase-Activity and Down-Regulates Vital Genes

et al. 2010

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ABSTRACT:The optimal oxygen concentration for newborn resuscitation is still discussed. Oxygen administration during reoxygenation may induce short-and long-term pathologic changes via oxidative stress and has been associated to later childhood cancer. The aim was to study changes in oxidative stress-associated markers in liver and lung tissue of newborn pigs after acute hypoxia followed by reoxygenation for 30 min with 21, 40, or 100% oxygen compared with room air or to ventilation with 100% oxygen without preceding hypoxia. Nine hours after resuscitation, we found a dose-dependent increase in the matrix metalloproteinase gelatinase activity in liver tissue related to percentage oxygen supply by resuscitation (100% versus 21%; p ϭ 0.002) pointing at more extensive tissue damage. Receiving 100% oxygen for 30 min without preceding hypoxia decreased the expression of VEGFR2 and TGFBR3 mRNA in liver tissue, but not in lung tissue. MMP-, VEGF-, and TGF␤-superfamily are vital for the development, growth, and functional integrity of most tissues and our data rise concern about both short-and longterm consequences of even a brief hyperoxic exposure. O ver the last two decades, the traditionally recommended use of 100% oxygen for newborn resuscitation has been extensively challenged. Meta-analyses have shown room air to be as efficient as 100% oxygen and that 100% oxygen increases both mortality and morbidity (1-3). In addition, an association has been found between newborn resuscitation with 100% oxygen and later childhood cancer (4,5) pointing at the outmost necessity to search for the underlying cause.Perinatal asphyxia may induce hypoxia-reoxygenation (HR) injury to various organs including liver and lungs, which have important roles in host defense after both organic and inorganic environmental insults (6). Liver-tissue responses to potentially damaging neonatal hypoxia and reoxygenation are of particular interest because of the unique and remarkable capacity of this organ to regenerate after injury via DNA replication and mitosis (7). The lungs are in a direct and continuous communication with the outside environment and are exposed directly to the highest partial pressure of inspired O 2. The time course of reactive oxygen species (ROS) generation during hypoxia and reperfusion is not clearly understood (8), but experimental evidence indicates a worsening of the hypoxic injury by reoxygenation (9,10). The underlying mechanisms of hypoxia induced liver or lung injury, and the nature of the detrimental biofactors set in motion these circumstances, are still poorly understood. Among the molecules whose expression and activity are modulated in tissue damage and repair are the matrix metalloproteinases (MMPs). MMPs belong to a family of zinc-containing endopeptidases best known for their roles in the physiologic and pathologic remodeling of the extracellular matrix (ECM) during angiogenesis, embryogenesis, wound healing, tumor metastasis, and various cardiovascular and inflammatory diseases (11). MMPs are important in...

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Increased lung matrix metalloproteinase-9 levels in extremely premature baboons with bronchopulmonary dysplasia

Cited by 47 publications

References 34 publications

Injury and repair in the very immature lung following brief mechanical ventilation

Injury and repair in the very immature lung following brief mechanical ventilation

Control Mechanisms of Lung Alveolar Development and Their Disorders in Bronchopulmonary Dysplasia

Resuscitation of Hypoxic Newborn Piglets With Supplementary Oxygen Induces Dose-Dependent Increase in Matrix Metalloproteinase-Activity and Down-Regulates Vital Genes

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