Propionyl-L-carnitine prevents the progression of atherosclerotic lesions in aged hyperlipemic rabbits

We have characterized the extent and the phenotype of total and proliferating 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 received the hypercholesterolemic diet alone or in addition to a treatment with propionyl-L-carnitine (PLC), a derivative of carnitine, an intramitochondrial carrier of fatty acids present in most cell types. We observed that, in both PLC-treated and control hyperlipemic rabbits, the ratio between proliferating macrophage-derived and smooth muscle cells was 2:1. PLC in addition to the hypercholesterolemic diet induced a marked lowering of plasma triglycerides, very low density lipoprotein (VLDL) and intermediate density lipoprotein (IDL) triglycerides, while plasma 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 macrophage-derived cells as compared to control hyperlipemic animals and a reduction of the number of both proliferating macrophage- and smooth muscle cell-derived foam cells. Finally, both proliferating and non-proliferating plaque cells expressed large amounts of macrophage colony-stimulating factor protein, in particular macrophage-derived foam cells. These results indicate that a modification of plasma lipemic pattern obtained by a long-term oral administration of PLC was associated with a decrease of plaque cell proliferation and severity of aortic atherosclerotic lesions.