Matrix metalloproteinases inhibition attenuates tobacco smoke-induced emphysema in Guinea pigs.

@article{Selman2003MatrixMI,
  title={Matrix metalloproteinases inhibition attenuates tobacco smoke-induced emphysema in Guinea pigs.},
  author={Mois{\'e}s Selman and Jos{\'e} Cisneros-Lira and Miguel Gaxiola and Remedios Ram{\'i}rez and Elizabeth M. Kudlacz and Peter G. Mitchell and Annie Pardo},
  journal={Chest},
  year={2003},
  volume={123 5},
  pages={
          1633-41
        }
}
STUDY OBJECTIVE To evaluate the effect of CP-471,474 (Pfizer Global Research and Development; Groton, CT), a broad-spectrum inhibitor of matrix metalloproteinases (MMPs) in an experimental model of emphysema. DESIGN Randomized, double-blinded, controlled experiment. SETTING Biochemistry and morphology laboratories and animal research facility. METHODS Guinea pigs were exposed to cigarette smoke over 1 month, 2 months, and 4 months, and half of the animals received CP-471,474. Age-matched… 
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References

SHOWING 1-10 OF 37 REFERENCES
Tobacco smoke-induced lung emphysema in guinea pigs is associated with increased interstitial collagenase.
TLDR
It is strongly suggested that increased interstitial collagen degradation plays a role in the development of lung emphysema.
Elevated levels of matrix metalloproteinases in bronchoalveolar lavage fluid of emphysematous patients.
TLDR
The presence of increased levels of matrix metalloproteinases in the lungs of patients with emphysema is demonstrated for the first time and it is suggested that, in BAL fluid, collagenase activity may be a better indicator of the presence of emphySEma than elastase.
Matrix metalloproteinases 2, 9, and 13, and tissue inhibitors of metalloproteinases 1 and 2 in experimental lung silicosis.
TLDR
It is suggested that an imbalance in the expression of MMPs and TIMPs may be implicated in extracellular matrix remodeling and basement membrane disruption during experimental lung silicosis.
Elastases and emphysema. Current assessment of the protease-antiprotease hypothesis.
  • A. Janoff
  • Biology, Medicine
    The American review of respiratory disease
  • 1985
TLDR
Assessments of lung elastase inhibitors in humans continue to support the importance of alpha-1-proteinase inhibitor in the protection of the lower respiratory tract, but newer information on locally produced, low molecular weight elastsase inhibitors indicates that these, too, may play a significant role.
Human collagenase (matrix metalloproteinase-1) expression in the lungs of patients with emphysema.
TLDR
The lung is altered in emphysema such that the Type II pneumocyte secretes MMP-1 and the induction of a proteolytic enzyme within the Type 2 pneumocyte suggests that the cells within the lung itself are capable of producing degradative enzymes in this disease process.
Cigarette smoking, emphysema, and damage to alpha 1-proteinase inhibitor.
TLDR
Almost two decades of research on mechanistic studies of damage to alpha 1-PI by cigarette smoke and phagocytic cells in vitro are reviewed, studies emphasizing the importance of elastinolytic activity in the pathogenesis of emphysema in vivo and studies of human lung lavage fluid to detect defects in alpha 2-PI at the molecular and functional levels are reviewed.
Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase- and cathepsin-dependent emphysema.
TLDR
It is demonstrated that IL-13 is a potent stimulator of MMP and cathepsin-based proteolytic pathways in the lung and causes emphysema with enhanced lung volumes and compliance, mucus metaplasia, and inflammation, when inducibly overexpressed in the adult murine lung.
Gelatinases A and B are up-regulated in rat lungs by subacute hyperoxia: pathogenetic implications.
Matrix metalloproteinase inhibition attenuates early left ventricular enlargement after experimental myocardial infarction in mice.
TLDR
Administration of an MMP inhibitor attenuates early left ventricular dilation after experimental MI in mice, and the effects of MMP inhibition on the changes in end-systolic area and end-diastolic area were most prominent in animals that had more initialleft ventricular dilatation.
Upregulation of gelatinases A and B, collagenases 1 and 2, and increased parenchymal cell death in COPD.
TLDR
Findings suggest that there is an upregulation of collagenase 1 and 2 and gelatinases A and B, and an increase in endothelial and epithelial cell death, which may contribute to the pathogenesis of COPD through the remodeling of airways and alveolar structures.
...
...