%0 Journal Article
%T Effects of MMP-9 inhibition by doxycycline on proteome of lungs in high tidal volume mechanical ventilation-induced acute lung injury
%A Adrian Doroszko
%A Thomas S Hurst
%A Dorota Polewicz
%A Jolanta Sawicka
%A Justyna Fert-Bober
%A David H Johnson
%A Grzegorz Sawicki
%J Proteome Science
%D 2010
%I BioMed Central
%R 10.1186/1477-5956-8-3
%X Mechanical function and gas exchange parameters improved following treatment with doxycycline in the high volume ventilated group as compared to the placebo group. Nine pulmonary proteins have shown significant changes between the two biochemically analysed (high volume ventilated) groups. Treatment with doxycycline resulted in a decrease of pulmonary MMP-9 activity as well as in an increase in the levels of soluble receptor for advanced glycation endproduct, apoliporotein A-I, peroxiredoxin II, four molecular forms of albumin and two unnamed proteins. Using the pharmacoproteomic approach we have shown that treatment with doxycycline leads to an increase in levels of several proteins, which could potentially be part of a defense mechanism.Administration of doxycycline might be a significant supportive therapeutic strategy in prevention of VILI.Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), are characterized by an acute inflammation and disruption of the alveolar-capillary membranes leading to alveolar flooding with protein-rich edema fluid. Mortality rates resulting from ALI and ARDS range from 18 to 54.7% [1]. Although mechanical ventilation (MV) is an important supportive strategy for patients with ARDS, it is also known to further lung injury in certain conditions of mechanical stress, leading to ventilation-induced lung injury (VILI). The mechanisms by which conventional MV exacerbates lung injury and inflammation are of considerable clinical significance. The potential importance of VILI in the clinical treatment of critically ill patients has been well established by recent clinical trials [2,3], where a relative risk reduction of 22% in patients ventilated with the lower tidal volume has been shown. The results from these studies indicate that mortality attributable to VILI is at least 9 to 10% in such patients. Therefore, despite the significant progress that has been recently made in emergency medicine, further
%U http://www.proteomesci.com/content/8/1/3