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Does a lipid nanoparticle carrying methotrexate, this nanoparticle carrying paclitaxel or a combination of both particles decrease graft vascular disease in rabbit herotopic transplanted hearts?
noedir stolf, Sr., Lucas Regatieri Barbieri, Domingos Filho Lourenco, Paulo Guitierriz, Elaine Tavares, Raul Maranhao.
heart institute univ sao paulo, sao paulo, Brazil.

OBJECTIVE: To evaluate the effect of a lipid nanopartide LDE - methotrexate LDE - paclitaxel and combination of both particles in graft vascular disease (GVD). To evaluate the influence of this treatment in the expression of genes involved in inflamatory response in a model of rabbit heart transplantation.
METHODS: Twenty-eight rabbits were submitted to heterotopic heart transplantation in the neck. All of them received cyclosporin and a diet enriched with colesterol.The preparation of a modified LDL lipid nanoparticle called LDE and incorporation of methotrexate and paclitaxel to LDE was previously described. The recipient rabbits were separated in 4 groups of seven animals: GroupI=LDE-methotrexate; GroupII=LDE-paclitaxel; GroupIII=both particles; GroupIV=control; The animals were sacrificed after 6 weeks. Ischemic transplantation time, basal and at the moment of sacrifice lipid profile, hematologic count, weight, ration ingestion were analyzed. It was performed imunohistochemistry for macrophage. Morphometry of coronary arteries of native and transplanted hearts were performed including area of internal elastic lamina, lumen area and calculation of percentage of stenosis. Expression of genes of inflamation cellular receptors and metalloproteinase in the myocardium was determined.
RESULTS: Weight variation, increase of colesterol ischemic time, ration ingestion was similar in all groups. The immunohistochemistry for macrophage showed significantly lower percentage of macrophage in the three treatment groups compared with control. In morphometry, there was no stenosis in of coronary arteries in native hearts. The mean stenosis of coronary arteries is higher in GroupIV and lowest in GroupII and intermediate in GroupI and GroupIII. The difference is significant between GroupII and control as well between groupII and GroupI and GroupIII. The analysis of genes of inflamatory response, cellular receptors and metalloproteinase showed variable results not consistent with an influence of treatment in decreasing inflamatory response.
CONCLUSIONS: In a model of heterotopic heart transplantation in rabbits: The treatment with GroupII decreases significantly GVD. The treatment with GroupII and treatment with combination of GroupI and groupII had a non significant decrease of GVD. The treatment with GroupIII. l had no toxic effect. The treatment had a variable effect in the expression of genes of inflamatory response.

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