Therapeutic neovascularization for peripheral arterial disease: in vivo models and potential therapeutic factors

Abstract

Peripheral arterial disease (PAD) is a major cause of morbidity and mortality. Therapeutic neovascularization is an alternative therapeutic strategy aimed at improving blood flow to the lower extremities and promoting blood vessel growth. The major components of neovascularization are; arteriogenesis and angiogenesis. These processes differ from each other. Arteriogenesis is initiated by shear stress and is the formation of collateral arteries from the pre-existing arteriolar network, and will mainly be found in the upper limb of the mice after ligation of the arteries in the limb. The molecular mechanism for arteriogenesis is based on shear stress regulated inflammatory responses, accompanied by the influx of inflammatory cells in the perivascular compartment around the collateral that are being formed. This thesis provides an analysis of two different in vivo models, the mouse hind limb ischemia (HLI) model and Matrigel plug assay. Furthermore, in the second part of this thesis, we focus on investigating the underlying mechanism of neovascularization in order to identify potential targets for therapeutic neovascularization.