This thesis describes the role of 14q32 microRNAs in vascular remodelling. The 14q32 microRNA cluster contains 54 microRNAs in humans and is highly conserved in mammals. In part I of this thesis,... Show moreThis thesis describes the role of 14q32 microRNAs in vascular remodelling. The 14q32 microRNA cluster contains 54 microRNAs in humans and is highly conserved in mammals. In part I of this thesis, we describe the role of 14q32 microRNAs in several processes of vascular remodelling. We have shown that inhibition of several 14q32 microRNAs, miR-329, miR-494 and miR-495, results in increased neovascularisation after hindlimb ischemia in mice. In addition, inhibition of the same microRNAs reduced atherosclerotic plaque formation and restenosis in experimental mouse models under hypercholesterolemic conditions. In part II of this thesis, we zoom in to the post-transcriptional regulation of 14q32 microRNAs through RNA binding proteins. The third and last part of this thesis studies the expression of microRNAs in subcutaneous adipose tissue of critical limb ischemia patients and discusses the potential use of microRNAs as biomarker to predict the risk of amputation in these patients. In conclusion, this thesis provides novel insights in the role of 14q32 microRNAs in processes of vascular remodelling. Experimental studies have identified 14q32 microRNAs as potential therapeutic targets for treatment and prevention of atherosclerosis, restenosis and peripheral arterial disease. Show less
The studies included in this thesis demonstrated a preclinical murine model to study neovascularization in vivo and subsequently a number of potential targets to stimulate therapeutic... Show moreThe studies included in this thesis demonstrated a preclinical murine model to study neovascularization in vivo and subsequently a number of potential targets to stimulate therapeutic neovascularization. This thesis contributes to a better insight into mechanisms underlying post-ischemic neovascularization and offers new therapeutic perspective to current treatment strategies for patients with critical limb ischemia. Whether stagnated blood flow recovery after an occlusive event is due to restricted pre-existing collateral bed or due to decreased collateral remodeling, we are now closer to a tailor made treatment available for each patient with peripheral arterial disease. Show less
