Inflammatory processes during arteriogenesis : the contribution of the innate immune system to collateral artery growth

The central theme of the work presented in the thesis is restoration of tissue perfusion by collateral artery growth. During collateral artery growth, or arteriogenesis, unused pre-existing vascular anastomoses remodel into functional arteries. These arteries are able to take over the perfusion of large areas when an arterial occlusion occurs by for instance atherosclerosis. The thesis starts with a short review of the current knowledge on the effects of classic cardiovascular risk factors for atherosclerosis on collateral artery growth. In the main part of the thesis we explore the role of the innate immune system in collateral artery growth, by studying TLR-2 en -4, Extra Domain A of fibronectin (EDA) and NF-?B in experimental models for arteriogenesis. Furthermore, we focus on improving the translation of experimental data from bench to bedside: we investigate the effects of aging on arteriogenesis and we present a new porcine model for coronary collateral artery growth. In the last chapter we use this model to characterize the effects of Celecoxib, a clinically available selective COX-2 inhibitor, on coronary collateral artery growth