Short-term atorvastatin treatment does not modify neointimal morphology but reduces MMP-2 expression in normocholesterolemic rabbit stented arteries.
The aim of our study was to explore some potential pleïotropic effects of atorvastatin, after stenting in the iliac arteries of normocholesterolemic rabbits. On day 0, 27 rabbits underwent stent implantation and were randomized into either the control group (standard chow, CTRL, n = 15) or the atorvastatin group (10 mg/kg/d per os, Ator, n = 12). On day 30, the stented arteries were harvested for histomorphometry and neointimal analysis [macrophages, matrix metalloproteinases (MMP-2), tissue inhibitor of metalloproteinase-2, vascular smooth muscle cells, and collagen]. Atorvastatin did not induce significant histomorphometric and inflammatory modifications but reduced neointimal expression of MMP-2 with no modification of tissue inhibitor of metalloproteinase-2, and also induced higher neointimal collagen content (Ator vs. CTRL: MMP-2: 0.05 +/- 0.03 vs. 0.70 +/- 0.20, P < 0.01; collagen: 17.0+/-0.7%/mm vs. 12.0 +/- 1.2%/mm(2) P < 0.01). Atorvastatin treatment also induced a significant decrease in neointimal vascular smooth muscle cells and cellular density (respectively: 2.0 +/- 0.2 vs. 1.4 +/- 0.2, P < 0.05; 5406 +/- 241 nuclei/mm(2) vs. 4402 +/- 163 nuclei/mm(2), P < 0.001). Our study provides new insights into the field of MMP response to stenting and the effects of statin therapy, which could have important implications in the field of in-stent restenosis.
Collin
Bertrand
B
Laboratory of Cardiovascular and Experimental Physiopathology and Pharmacology, Faculty of Medicine, University of Burgundy, 7 Bd Jeanne d'Arc, France. bertrand_collin@hotmail.com
Busseuil
David
D
Korandji
Claudia
C
Zeller
Marianne
M
Cottin
Yves
Y
Duvillard
Laurence
L
Rioufol
Gilles
G
Pitois-Merli
Isabelle
I
Rochette
Luc
L
D000818:Animals; D000069059:Atorvastatin; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000188:drug therapy; D007083:Iliac Artery / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis*; D009131:Muscle, Smooth, Vascular / Q000737:chemistry; D011758:Pyrroles / Q000494:pharmacology*; D011817:Rabbits; D015607:Stents; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis; D017539:Tunica Intima / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D019716:Tissue Inhibitor of Metalloproteinase-2; D000069059:Atorvastatin; D020778:Matrix Metalloproteinase 2