It is believed that emphysema in smokers is mediated by

It is believed that emphysema in smokers is mediated by proteases released from inflammatory L 012 sodium salt that cause destruction of the extracellular matrix in alveolar septa [1]. Metalloprotease-12 is mainly released by macrophages and is considered the enzyme responsible for emphysematous lesions in experimental rodent models [6,7]. Rodrigues et al. [46] induced emphysema in mice with elastase and observed increases in Lm, the number of macrophages in tissue, and MMP-12-positive cells. We also observed an increase in lung destruction (as measured by Lm), a greater number of macrophages in the tissue, and increased expression of MMP-12 in this group with respect to the control group. The A5 mg and A20 mg groups showed a significant reduction of MMP-12 expression compared with the PPE 64d group; however, the 1 mg group was similar to the PPE 64d group. In a model of emphysema, Takahashi et al. [18] concluded that simvastatin reduced the expression of MMP-12 in the lung, as well as the number of neutrophils and lymphocytes. In addition, the concentration of TNF-α in the bronchoalveolar lavage indicated a reduction of inflammation. Our study has two major limitations. First, although atorvastatin treatment was able to induce an increase in the amounts of collagen and elastic fibers, we cannot conclude that this treatment reduced the lung damage since we not perform measurements to evaluate whether this parenchymal remodeling was beneficial for maintaining the efficiency of lung function and suitable gas exchange. Studies investigating emphysema have shown an increase in the amounts of collagen and elastin after disease development [[47], [48], [49], [50]]. However, the newly deposited elastin and collagen fibers undergo substantially larger distortions than in normal tissue, and lower mechanical forces applied to this tissue during the respiratory process are sufficient to cause tissue destruction and emphysema progression. Changes in lung extracellular matrix components could impair the mechanical properties of the lung (as cited above). We failed to evaluate the different components of the extracellular matrix in lungs, especially collagens I and III, as well as to evaluate the mechanical respiratory parameters to attest if this increase in elastic and collagen fibers after treatment with atorvastatin was beneficial for lung function. Second, we did not evaluate a control group treated with atorvastatin to explore side effects related to this drug. However, in a previous experiment, we treated a control group of mice with atorvastatin for 60 days and observed no changes in lung and liver [20]. Thus, these two limitations do not invalidate the experimental design and results presented herein.
Conclusions
Introduction Emphysema is a type of chronic obstructive pulmonary disease (COPD) and is a worldwide public health problem that reduces quality of life (Hogg and Timens, 2009). Emphysema is characterised by airspace enlargements and is accompanied by destruction of the parenchymal structure (Snider, 1989). The causes of emphysema in humans are cigarette smoke, environmental irritants, genetic factors and indoor pollutants (Barnes, 2000); these factors result in general decrements in health that include weight loss, muscle atrophy, changes in muscle fibre type and systemic inflammation (Langen et al., 2006). Emphysema leads to death, and there is currently no cure. The emphysema observed in smokers begins in the respiratory bronchioles near the thickened and narrowed small bronchioles that become the major site of obstruction in COPD (Hogg and Timens, 2009). The physiological manifestations of the disease include impaired gas exchange (due to loss of alveolar surface area), limited airflow, increased lung compliance and increased effort required to breathe (Hogg, 2004). Because cigarette smoke is the main cause of emphysema in humans, experimental animal models have attempted to reproduce this situation (Churg et al., 2008). Elastolytic enzymes have been shown to reproduce some characteristics of human cigarette smoke-induced disease (Breuer et al., 1993; Ito et al., 2005).