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

• Published in: Atherosclerosis 1995-04, Vol.114 (1), p.29-44
• Main Authors: Spagnoli, Luigi Giusto, Orlandi, Augusto, Marino, Bonaventura, Mauriello, Alessandro, De Angelis, Clara, Ramacci, Maria Teresa
• Format: Article
• Language: English
• Subjects: Aging; Animals; Arteriosclerosis - metabolism; Arteriosclerosis - pathology; Arteriosclerosis - prevention & control; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Carnitine - administration & dosage; Carnitine - analogs & derivatives; Carnitine - pharmacology; Cell Division - drug effects; Cell proliferation; Diet; Disease Models, Animal; Female; Foam Cells - pathology; Hyperlipidemias - metabolism; Hyperlipidemias - pathology; Hyperlipidemias - prevention & control; Immunohistochemistry; Lipoproteins, VLDL - metabolism; Macrophage; Male; Medical sciences; Muscle, Smooth, Vascular - pathology; Propionyl-L-carnitine; Rabbit; Rabbits; Smooth muscle cell; Triglycerides
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/0021-9150(94)05460-Z

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.