Collateral development in limb ischemia : Aspects of endogenous and stimulated arteriogenesis

摘要: Peripheral arterial disease (PAD) is common among elderly and affects about 20% of the population above age 60 years. PAD a strong marker for future cardiovascular events increased mortality due to widespread atherosclerotic lesions in coronary cerebral arteries. Intermittent claudication (IC) with lower extremity pain on walking has prevalence 3-6 % men at 60-70 years according large studies. Among these patients majority remain stable without progression symptoms. The symptoms progress 25% distal ulceration or gangrene ischemic rest pain, i.e critical limb ischemia (CLI) develops. Despite liberal indications surgical endovascular revascularizations, major amputation required as much one third CLI there great need alternative treatment strategies. Collateral development, bridging stenoses occlusions, reparative processes that reduce consequences artery PAD. growth collaterals from preexisting arteriole called arteriogenesis. Angiogenesis, sprouting new capillaries, may also be importance pathophysiology There little data establishing any impact angiogenesis but it likely an angiogenic process occurs tissues response acute ischemia. Accordingly, hemodynamic forces, cytokines inflammatory appear arteriogenesis, exact role not firmly established. arteriogenic mechanisms studied animal models vitro aiming stimulate arteriogenesis by supplying vascular factors have shown promising results. aim this thesis was assess patients, furthermore evaluate gene therapy FGF-4 model humans method therapeutic First we explored expression skin muscle samples 25 CLI. were levels FGF-2 VEGF compared proximal. Furthermore investigated 20 IC after provocation. pro-inflammatory cytokine IL-6 significantly elevated hour exercise. mRNA Taken together results indicate rises locally maximal exercise absolute limit rest. seems upregulated which could local processes. Gene adenovirus mediated assessed rat severe phase I/II multicenter clinical trial patients. No signs stimulated detected 4 weeks transfer. 13 seemed safe, no sign able small patient cohort.