Abstract 360: Reduction of Atherosclerotic Lesions by the Chemotherapeutic Agent Carmustine Associated to a Lipid Nanoemulsion

Abstract

After injection in bloodstream, a lipid nanoemulsion (LDE) resembling low-density lipoprotein (LDL) concentrate in atherosclerotic lesions of cholesterol-fed rabbits. Here, rabbits with atherosclerosis were treated with carmustine, an antiproliferative agent used in cancer chemotherapy, associated to LDE to investigate the effects on the lesions. Eighteen male New Zealand rabbits were fed a 1% cholesterol diet for 8 weeks. After 4 weeks nine animals were treated intravenous saline solution and nine with intravenous LDE-carmustine (4 mg/kg, weekly for 4 weeks). LDE-carmustine inhibited atherosclerotic lesions by 90%, compared to controls. LDE-carmustine reduced presence of macrophages, smooth muscle cells, and regulatory T-cells in the arterial intima as well as the expression of matrix metallopeptidase-9, interleukin-1β and TNF-α and lipoprotein receptors (LDL receptor, LDL-related protein-1 and scavenger receptor class B member 1). In conclusion, LDE-carmustine treatment resulted in marked reduction of lesion area, invasion by macrophages and intimal smooth muscle cells and pro-inflammatory factors. Therefore, this new formulation shows great potential for therapy of atherosclerotic cardiovascular disease.