AbstractsBiology & Animal Science

In the current thesis, spatio-temporal evaluation of the endogenous angiogenic response to ischemia was perfomed. After vascular occlusion, ischemic angiogenesis is an important reparative mechanism and can ameliorate the outcome of ischemic disease. Diabetic foot ulcers affect almost 15% of diabetic patients and are the leading cause of amputations worldwide. Numerous studies have confirmed the impaired post-ischemic angiogenesis in diabetes. Consequently, wound healing patterns are disturbed in diabetes mainly due to decreased ischemia-driven angiogenesis. Integrin ανβ3 is a promising imaging target of angiogenic activity which is up-regulated on activated endothelial cells (ECs) but not on quiescent ones. Molecular imaging (MI) of ανβ3 integrin expression with the aid of a dedicated high resolution gamma camera, is a very sensitive imaging approach for the evaluation of angiogenesis in the rabbit hindlimb ischemia model. Furthermore, diabetes mellitus (DM) was induced, to study the effects of this pathology on the spatio-temporal distribution of angiogenesis. In order to evaluate the whole spectrum of endogenous process of collateralization after occlusion of an artery, Digital Subtraction Angiography (DSA) was also used for the visualization of larger collaterals. During the first part of the study DM experimental protocol was investigated in order to find the appropriate protocol for the induction of long-term diabetic animal model, as it is a methodology that has not yet been standardized. At the same time a cohort of animals underwent endovascular embolization for the establishment of hindlimb ischemia and were imaged with the aid of a MI radiotracer technique in order to deal with unresolved issues and establish the imaging protocol. The study included seven New Zealand White (NZW) rabbits that underwent unilateral percutaneous endovascular embolization of the femoral artery, for the establishment of hindlimb ischemia that triggers the endogenous process of collateralization. The contralateral limb was not embolized and served as a control. The employed radiotracer for angiogenesis imaging, was a 99mTc labeled cyclic RGD peptide [c RGDfk-His]-99mTc that binds specifically to ανβ3 integrin via the three amino acid sequence Arginine-Glycine-Aspartic acid or RGD. Image acquisition was performed with a high resolution gamma camera and all animals underwent molecular imaging on the 3rd and the 9th day post-embolization. In all animals DSA was performed on the 9th day post-embolization.Angiogenesis was successfully detected using a 99mTc labeled cyclic RGD peptide MI technique and was significantly more pronounced in the ischemic compared to normal limbs, both at day 3 and day 9 after embolization. The peak of the phenomenon was detected at day 9. Increased mean vessel length in the normal compared to the ischemic limb demonstrates that although angiogenesis is pronounced in day 9, arteriogenesis is not sufficiently pronounced and that the phenomenon of arteriogenesis has just initiated. Σκοπός της παρούσας…