Abstract 11952: Daunorubicin Associated With Lipid Nanoparticles Reduces Inflammation and Aortic Lesions in an Atherosclerosis Rabbit Model

التفاصيل البيبلوغرافية
العنوان: Abstract 11952: Daunorubicin Associated With Lipid Nanoparticles Reduces Inflammation and Aortic Lesions in an Atherosclerosis Rabbit Model
المؤلفون: Albuquerque, Camila I, Tavares, Elaine R, Guido, Maria Carolina, Lopes, Natalia M, Vanalli Baroni, Roberta, Jensen, Leonardo, Araujo Silva, Bruna M, Kalil, Roberto, Tavoni, Thauany M, Maranhao, Raul C
المصدر: Circulation (Ovid); November 2019, Vol. 140 Issue: Supplement 1 pA11952-A11952, 1p
مستخلص: Introduction:Nanoparticles that resemble the lipid structure of LDL, named LDE, concentrates on sites with high cell proliferation rates, as in atherosclerotic lesions. Chemotherapeutic agents have been associated to this vehicle in experimental and clinical protocols. Daunorubicin (DNR) is an antiproliferative chemotherapeutic agent and its association to LDE has already been studied in a mouse cancer model, showing no relevant toxicity.Hypothesis:To investigate the efficacy of the treatment with DNR associated to LDE in a rabbit model of atherosclerosis induced by a high cholesterol diet.Methods:New Zealand male rabbits were fed with a 1% cholesterol diet for 8 weeks to induce atherosclerosis. After 4 weeks, the animals were treated weekly with LDE-DNR (6mg/kg, iv, n=6) or with LDE only (n=6). In addition, 3 animals without any intervention were used as a control group. Chow consumption, lipid and hematological profiles, body weight, and echocardiography were evaluated at baseline, pre-treatment and post-treatment. Morphometry and protein expression were performed to analyze the aortas.Results:There was no difference in food intake and body weight for control, LDE and LDE-DNR groups. Total cholesterol, HDL-C, non-HDL-C and triglycerides increased in LDE and LDE-DNR groups at baseline when compared to post-treatment. Red blood cells decreased in LDE group at post-treatment in comparison to baseline, while LDE-DNR presented no such difference. Echocardiographic analysis showed no difference between groups and periods. However, LDE showed a significant increase in relative heart weight compared to control. Regarding aortic lesions, LDE-DNR group was 50% lower than LDE group. The protein expression of the inflammatory markers CD68, TNF-?, IL-6 and NF-?B in LDE-DNR was lower than LDE. Pro-apoptotic factors caspase 3, caspase 9 and BAX were also lower in LDE-DNR compared to LDE.Conclusions:Treatment with LDE-DNR reduced aortic lesions, diminished both inflammatory and pro-apoptotic factors and promoted cardiac preservation in a rabbit atherosclerosis model. The treatment with LDE-DNR did not induce observable hematological toxicity.
قاعدة البيانات: Supplemental Index
الوصف
تدمد:00097322
15244539
DOI:10.1161/circ.140.suppl_1.11952