PROPIONYL-L-CARNITINE PREVENTS THE PROGRESSION OF ATHEROSCLEROTIC LESIONS IN AGED HYPERLIPEMIC RABBITS

We have characterized the extent and the phenotype of total and prolif erating cell population of aortic plaques in aged rabbits receiving a long-term low-dose cholesterol hyperlipemic diet, which represents an experimental model of atherosclerosis. For nine months, rabbits receiv ed the hypercholesterolemic diet alone or in addition to a treatment w ith propionyl-l-carnitine (PLC), a derivative of carnitine, an intrami tochondrial carrier of fatty acids present in most cell types. We obse rved that, in both PLC-treated and control hyperlipemic rabbits, the r atio between proliferating macrophage-derived and smooth muscle cells was 2:1. PLC in addition to the hypercholesterolemic diet induced a ma rked lowering of plasma triglycerides, very low density lipoprotein (V LDL) and intermediate density lipoprotein (IDL) triglycerides, while p lasma cholesterol was slightly and transiently reduced. Moreover, PLC- treated hyperlipemic rabbits exhibited a reduction of plaque thickness and extent, a slight but significant reduction of the percentage of m acrophage-derived cells as compared to control hyperlipemic animals ac id a reduction of the number of both proliferating macrophage- and smo oth muscle cell-derived foam cells. Finally, both proliferating and no n-proliferating plaque cells expressed large amounts of macrophage col ony-stimulating factor protein, in particular macrophage-derived foam cells. These results indicate that a modification of plasma lipemic pa ttern obtained by a long-term oral administration of PLC was associate d with a decrease of plaque cell proliferation and severity of aortic atherosclerotic lesions.