Rajaram, Jessica Indira (2016) The renin-angiotensin system enzymes in chronic obstructive pulmonary disease. University of Southampton, Faculty of Medicine, Doctoral Thesis, 163pp.
Abstract
Introduction: Chronic obstructive pulmonary disease (COPD) is the third leading cause of mortality in the world. As this disease is progressive in its nature, patients suffer a gradual decline in their quality of life due to a progressive deterioration in lung function.
Although there are treatments available to alleviate COPD symptoms, there is no pharmacological treatment that stops the decline in lung function within the lungs of COPD patients. Literature has suggested that angiotensin-converting enzyme inhibitors (ACEi) could potentially reverse lung decline but there is limited research into angiotensin-converting enzyme (ACE) in COPD lung. The work in this thesis investigated lung ACE as well as other enzymes associated with the renin-angiotensin system (RAS) within the lungs of COPD patients.
Methods: Lung samples were taken from subjects undergoing surgery. These subjects were classified according to their lung function into groups of COPD (n=36) or nonCOPD (n=34). The lung samples were evaluated for the localisation, abundance and activity of enzymes that are associated with the production of RAS peptides: ACE, chymase, renin and ACE-2. This was by immunohistochemistry and enzymatic assays. The number of positive cells/vessels and the activity of these enzymes were measured in COPD lung and compared to subjects without COPD. The effects of ACEi prescribed to these subjects as well as their smoking status on lung enzyme expression and activity were also investigated.
Results: ACE activity was significantly lower in the lungs of COPD subjects compared to subjects without COPD. For the first time, ACE-2 staining was observed in macrophages from lung tissue as well as monocyte-derived macrophages (Mdm) and this human ACE-2 protein seemed catalytically active. ACE-2 activity and expression seemed to be higher in COPD and also in smokers compared to controls however this was not significant.
Conclusions: The activity of the RAS is overlooked as a potential risk factor for COPD. The work in this thesis has identified that the RAS enzyme ACE is linked with COPD and could be a target for pharmacological treatment of lung decline observed in COPD in the future. Another enzyme of the RAS, ACE-2 is localised to the lung macrophage, which is a cell associated with the inflammatory response. This finding could spark research into the function of ACE-2 in the macrophage and ACE-2 expression modification may be beneficial for inflammatory disease such as COPD in the future.
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- Faculties (pre 2018 reorg) > Faculty of Medicine (pre 2018 reorg) > Clinical & Experimental Sciences (pre 2018 reorg)
Current Faculties > Faculty of Medicine > Clinical and Experimental Sciences > Clinical & Experimental Sciences (pre 2018 reorg)
Clinical and Experimental Sciences > Clinical & Experimental Sciences (pre 2018 reorg)
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