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.
Orlandi
Augusto
A
Department of Biopathology and Image Diagnostics, Anatomic Pathology Institute, Tor Vergata University of Rome, Via della Ricerca Scientifica, 00133 Rome, Italy.
Marcellini
Marcella
M
Pesce
Daniela
D
Calvani
Menotti
M
Spagnoli
Luigi Giusto
LG
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000097:blood; D002331:Carnitine / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use*; D002339:Carotid Arteries / Q000473:pathology*; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects*; D002784:Cholesterol / Q000097:blood; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000187:drug effects / Q000201:enzymology; D006965:Hyperplasia / Q000188:drug therapy / Q000201:enzymology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D011817:Rabbits; D014280:Triglycerides / Q000097:blood; D017539:Tunica Intima / Q000201:enzymology* / Q000473:pathology* / Q000648:ultrastructure
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D014280:Triglycerides; C003223:propionylcarnitine; D002784:Cholesterol; D053148:Caspase 3; D020169:Caspases; D002331:Carnitine