Endothelium restenosis

Nanoparticles formulated with PLGA have been shown to be rapidly uptaken by the endothelial cells, the uptake was shown to depend on the nanoparticle concentration and the particles where mainly shown to localize in the cytoplasm (207). These nanoparticles were also shown to be biocompatible with the cells with no effect on cell viability (207). This is important due to the fact that endothelium is an important target for gene therapy in a number of disorders including angiogenesis, atherosclerosis, tumor growth, myocardial infarction, limb and cardiac ischemia, restenosis (207). 

NO plays multiple roles in the arterial wall, which are dilatation of the artery, inhibition of platelet aggregation, prevention of adhesion of leukocyte with endothelium, and suppression of growth of VSMC. Multiple factors are involved in the induction of restenosis, so that the strategy to augment NO production may be the most practical approach for its treatment. 

Duffy et al, (2) showed that DFO improved endothelium-dependent vasodilatation in patients with coronary artery disease. In his review of 68 references regarding iron-mediated cardiovascular injury, F-lorwitz and Rosenthal (47) concluded that iron chelation may prevent restenosis and atherogenesis in coronary arteries, Paraskevaidis et al. (48)... 

An intact endothelium acts as a physical barrier to platelets adhesion. 4s well as causing vessel thrombosis, platelets produce factors that stimulate smooth muscle cells, leading to restenosis. 

A narrowing of the blood vessels (restenosis) often occurs after coronary blood vessel dilatation by stent implantation. This is probably caused by the proliferation of smooth muscle cells following injuring of the blood vessel endothelium by the stent. Here, the role of adenoviral or plasmid DNA-mediated transfer of the gene encoding inducible nitroxid synthase (iNOS) is thought to result in reduced cell proliferation. 

On the basis of the therapeutic efficacy of this strategy, we obtained permission for a second clinical trial (starting in 2002) using the decoy strategy to treat restenosis. In this trial, NF-kB decoy ODN was delivered to the vessel wall through a hydrogel-coated catheter without any viral or nonviral vector. Efficient ODN transfection was confirmed with fluorescein isothiocyanate (FlTC)-labeled ODN. The hydrogel-coated catheter was able to deliver the ODN not only to the coronary endothelium, but also to the vascular wall [18]. 

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