Abstract 13994: Anti-cellular Proliferation Therapy Reduces Atherosclerotic Plaques and Vascular Inflammation in Experimental Hypercholesterolemia

Abstract

Introduction: The lipid nanoemulsion (LDE) binds intensely to LDL receptors due to similarity in molecular composition. Anti-proliferative agents paclitaxel (PTX) and methotrexate (MTX) may have beneficial effects on atherosclerosis by preventing proliferation of inflammatory cells and vascular smooth muscle cells. Hypothesis: By combining LDE to PTX and MTX, effective regression of hypercholesterolemic atherosclerosis and vascular inflammation occurs. Methods: Rabbits underwent induction of atherosclerosis by consuming a cholesterol diet for 8 weeks. Afterwards, 7 rabbits were sacrificed and had their aortas analyzed (Control group). The other rabbits had diet replaced by regular diet, and were divided into 3 groups (n=7 each), according to the 8-week treatment offered: LDE-PTX, LDE-PTX+MTX and Diet (no agent). The rabbits were then sacrificed and the aortas analyzed. Vascular tumor necrosis factor-α (TNF) gene expression was determined in all aorta samples. Results: See graph. LDE-PTX and LDE-PTX+MTX treatments presented marked gross regressions of plaque areas when compared to Control. Diet treatment alone did not reduce significantly plaque area. Regarding TNF gene expression, Control group presented 1.70±1.01 mRNA levels while LDE-PTX, LDE-PTX+MTX and diet alone groups presented 1.01±0.03, 0.31±0.10 and 0.20±0.09 levels (p<0.01 ANOVA). All 3 treatment groups produced significant decrease in LDL blood levels. Conclusions: Therefore, this study demonstrates that anti-cellular proliferation by PTX+MTX, combined to LDE, produces marked gross atherosclerotic regression and beneficial effect on vascular inflammation.