Mouse models of chronic obstructive pulmonary disease : in search of novel treatment options

Abstract

Chronic Obstructive Pulmonary Disease (COPD) is currently the third leading cause of death worldwide and the prevalence is expected to rise further. COPD patients often suffer from comorbidities including lung cancer, osteoporosis, skeletal muscle dysfunction, depression, gastrointestinal diseases, metabolic syndrome and cardiovascular diseases (CVD) in addition to the pulmonary features. Especially CVD, mainly caused by atherosclerosis, is an important cause of morbidity and mortality in COPD patients. Dyslipidemia and systemic inflammation are important risk factors for atherosclerosis. COPD patients have an increased risk to develop atherosclerosis compared to matched controls. Although smoking cessation is important to limit the progression of the disease, there is a higher risk to develop COPD and atherosclerosis even after smoking cessation. There are several mechanisms which may explain the link between COPD and atherosclerosis, including dietary habits and dyslipidemia, infections, inflammation, oxidative stress and endothelial dysfunction. Recent data indicate that brown adipose tissue (BAT) contributes not only to lipoprotein metabolism, but BAT activation also may inhibit atherosclerosis development. Mouse models provide good platform to study COPD or atherosclerosis, but also atherosclerosis and COPD combined. Therefore, in this thesis we focussed on mouse models for COPD and CVD, and their use in development of new treatments