In peripheral arterial occlusive disease (PAOD), the formation of an atherosclerotic lesion eventually results in a significant stenosis of a major artery thereby disrupting blood flow in... Show moreIn peripheral arterial occlusive disease (PAOD), the formation of an atherosclerotic lesion eventually results in a significant stenosis of a major artery thereby disrupting blood flow in peripheral arteries towards lower limb tissue. Unfortunately, there is a substantial number of patients that suffer from severe critical limb ischemia, which is associated with a poor prognosis and high rates of amputation and mortality. Despite state-of-the-art revascularization treatment options and optimal control of co-morbidities these 'no option' patients remain at high risk for limb amputation. It is these patients that require new therapeutic applications to augment neovascularization and prevent them from limb amputation. Expansion of our current knowledge is required to gain insight in cellular and molecular mechanisms that are involved in neovascularization, to optimize revascularization therapies for patients with critical limb ischemia. This thesis provides a role for multiple leukocytes in blood flow recovery, in particular Natural Killer cells and CD4+ T lymphocytes, and shows that genetic differences in the Natural Killer gene complex induce differences in vascular remodeling. It was also shown how growth factor expression, signaling and regulation of gene expression modulate revascularization. Show less
Peripheral artery disease (PAD) remains a major cause of morbidity and mortality in the Western world. Therapeutic strategies to obtain revascularization of affected limbs are frequently needed in... Show morePeripheral artery disease (PAD) remains a major cause of morbidity and mortality in the Western world. Therapeutic strategies to obtain revascularization of affected limbs are frequently needed in these patients. Unfortunately, the initial success of surgical and/or endovascular revascularization can be threatened by progressive disease ultimately leading to an amputation. A better understanding of the complex cellular and molecular processes involved in post-ischemic neovascularization may reveal novel options for therapeutic interventions for PAD patients. This thesis describes reports that contribute to an increase in the knowledge and insights into different cell types involved in collateral artery growth in limb ischemia with the aim of developing new therapeutic strategies for PAD. Show less
