This thesis focuses on the relationship between smoking and macrophages in chronic obstructive pulmonary disease (COPD), and on treatment with inhaled corticosteroids (ICS). Macrophages play an... Show moreThis thesis focuses on the relationship between smoking and macrophages in chronic obstructive pulmonary disease (COPD), and on treatment with inhaled corticosteroids (ICS). Macrophages play an important role in COPD, and constitute a heterogeneous population with pro- (Mf1) and anti-inflammatory (Mf2) cells. This thesis evaluated YKL-40 and CD163 as markers for Mf1 and Mf2, respectively. Peripheral airways contained more CD163-positive Mf2 compared to central airways. Smoking cessation skewed the macrophage phenotype towards Mf2 in the peripheral airways, but did not influence YKL-40 levels in sputum. Whereas smoking can induce structural alterations in extracellular matrix (ECM) components in the airways, no differences in ECM components in bronchial biopsies were found between current and ex-smokers with COPD. ICS treatment attenuates lung function decline and decreases airway inflammation in a subgroup of COPD patients. However, long-term ICS treatment did not change YKL-40 levels in sputum and serum. ICS increased deposition of several ECM proteins in the airways, which was correlated with improved lung function, suggesting prevention of airway collapse. Withdrawal of ICS after long-term treatment induced a relapse in lung function decline and increased airway inflammation in bronchial biopsies and sputum, suggesting that benefits of ICS do not persist after discontinuation of ICS. Show less
Vein graft surgery to treat occlusive arterial disease is a common applied procedure. Each year more than two million vein graft surgeries are performed worldwide. The major drawback of vein... Show moreVein graft surgery to treat occlusive arterial disease is a common applied procedure. Each year more than two million vein graft surgeries are performed worldwide. The major drawback of vein grafting is that within 10 years after vein graft surgery 50-60 % of the vein grafts suffer from patency loss due to thrombosis, intimal hyperplasia formation, accelerated atherosclerosis and rupture. Endogenous factors orchestrate the development and failure of vein grafts. Investigating the role of endogenous constituents on vein graft remodeling can enhance our basic knowledge of the involvement of these factors in vein graft remodeling. By interfering in the function of endogenous factors, as we showed in this thesis, vein graft remodeling can be negatively or positively influenced depending on the factor and strategy used. New therapeutic strategies can be developed based on this knowledge. In this thesis we investigate the role of innate immune components, complement system factors, toll like receptors, mast cells and NK cells and the role of Annexin A5 in vein graft remodeling. Furthermore we explored the role of plaque stability, plaque neovascularization and extracellular matrix remodeling in a hypercholersterolemic mouse vein graft model. Show less
