Effect of clopidogrel on neointimal formation and inflammation in balloon-denuded and radiated hypercholesterolemic rabbit iliac arteries.
BACKGROUND
Platelet-derived peptide and nonpeptide growth factors are known to play pivotal roles in neointimal proliferation. Along with its antiplatelet activity of reducing P-selectin and hs-CRP, clopidogrel has also been shown to have anti-inflammatory properties. The aim of this study is to find out by modulating inflammation if clopidogrel can affect neointima formation in balloon-denuded iliac arteries of hypercholesterolemic rabbits.


RESULTS
Rabbits were fed with 1% cholesterol diet with (n = 20) or without (n = 20) clopidogrel (10 mg/kg body weight) for 7 days followed by balloon-denudation of endothelial layer in both the iliac arteries and continued on 0.15% cholesterol diet with or without clopidogrel. Four weeks later, the denuded area in both iliac arteries was radiated (n = 11, cholesterol-only group; n = 9, clopidogrel group) or sham treated (n = 10 from each group). Four weeks after radiation, animals were sacrificed and arterial segments were processed for morphometry. In the sham-treated clopidogrel group, neointimal area, percent stenosis, and macrophage score were 39% (P = 0.01), 32% (P = 0.02), and 50% (P = 0.02) smaller, respectively, when compared to the cholesterol-only group (0.48 +/- 0.18, 32.42 +/- 13.04, and 1.5 +/- 0.83). There were no differences in the radiated group (0.89 +/- 0.32, 50.34 +/- 13.00, and 1.88 +/- 1.27 vs. 0.93 +/- 0.38, 59.41 +/- 11.41, and 2.00 +/- 0.74, respectively).


CONCLUSIONS
This study demonstrates that clopidogrel reduces inflammation and neointimal formation in balloon-denuded iliac arteries of hypercholesterolemic rabbits.
Waksman
Ron
R
Cardiovascular Research Institute, Washington Hospital Center, Washington, DC 20010, USA. ron.waksman@medstar.net
Pakala
Rajbabu
R
Roy
Probal
P
Baffour
Richard
R
Hellinga
David
D
Seabron
Rufus
R
Chan
Rosanna
R
Scheinowitz
Mickey
M
Kolodgie
Frank
F
Virmani
Renu
R
D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D002097:C-Reactive Protein / Q000187:drug effects; D000077144:Clopidogrel; D004730:Endothelium, Vascular / Q000187:drug effects / Q000528:radiation effects; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000503:physiopathology* / Q000532:radiotherapy; D007083:Iliac Artery / Q000187:drug effects* / Q000528:radiation effects; D007249:Inflammation / Q000188:drug therapy*; D008264:Macrophages; D008297:Male; D019007:P-Selectin / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011817:Rabbits; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017539:Tunica Intima / Q000187:drug effects*
D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D002097:C-Reactive Protein; D000077144:Clopidogrel; D013988:Ticlopidine