Emphysema is caused by a protease-antiprotease imbalance and by failing maintenance mechanisms. Repair genes are upregulated in COPD lungs, but restoration nevertheless fails. Copper (Cu) is an essential cofactor in… Click to show full abstract
Emphysema is caused by a protease-antiprotease imbalance and by failing maintenance mechanisms. Repair genes are upregulated in COPD lungs, but restoration nevertheless fails. Copper (Cu) is an essential cofactor in the last step of collagen/elastic fibre repair, i.e. crosslinking by lysyl oxidases. Based on animal models suggesting that emphysema formation induces copper deficiency and vice versa, it may be suspected that copper supplementation would restore repair mechanisms. Since Cu monotherapy would stimulate fibrosis formation, Cu may be combined with heparin (hep) as a specific inhibitor of collagen crosslinking and stimulator of elastin polymerization. Precision-cut lung slices from wild-type mice (n=6) were used to assess the effect of Cu-hep on elastase-induced parenchymal destruction. Slices were treated with elastase (2.5 µg/ml) for 16h and Cu-hep for 16h or 40h, after which linear mean intercept (LMI) was assessed as a surrogate for alveolar enlargement. LMI was increased in the elastase compared to the control group (p
               
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