Propionyl-L-carnitine reduces intimal hyperplasia after injury in normocholesterolemic rabbit carotid artery by modulating proliferation and caspase 3-dependent apoptosis of vascular smooth muscle cells

Previously we documented that propionyl-L-carnitine (PLC) reduces the growth of atherosclerotic lesions in cholesterol-fed aged rabbits in association with a decrease of plaque smooth muscle cell (SMC) proliferation and plasma triglycerides. To clarify whether PLC might influence SMC growth through mechanisms other than triglyceride lowering, we investigated the effect of a daily treatment per os with PLC on carotid intimal hyperplasia after ballooning in normocholesterolemic rabbits. PLC did not induce variations of plasma triglyceride and cholesterol. One week later, the number of proliferating SMCs was reduced in PLC as compared with controls. After 3 weeks, morphometric analysis demonstrated a reduced neointimal relative volume and percentage of stenosis but not vessel area in PLC as compared with controls. This associated with an intimal reduced SMC number and an increased apoptotic rate as detected by nick-end labelling (TUNEL) and ligation-mediated polymerase chain reaction (PCR). Western blotting also demonstrated an increase of caspase-3 cleavage in PLC carotids. Antiproliferative and pro-apoptotic effects of PLC were confirmed in vitro on actively proliferating and serum deprived SMCs. respectively. Molecules with an additional cell-specific. pro-apoptotic action may represent a new therapeutic tool in reducing intimal SMC hyperplasia following angioplasty or stenting procedures. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.