Metalloproteinase inhibition reduces constrictive arterial remodeling after balloon angioplasty: a study in the atherosclerotic Yucatan micropig.
BACKGROUND
Arterial remodeling after balloon angioplasty has been recognized as a major determinant of restenosis. Perturbation of collagen metabolism might be important. After balloon injury, matrix metalloproteinase (MMP) expression is upregulated. We investigated the effect of Batimastat, a nonspecific MMP inhibitor, on late lumen loss, arterial remodeling, and neointima formation after balloon dilation.


RESULTS
In atherosclerotic iliac arteries of 12 Yucatan micropigs, balloon dilation was performed, with intravascular ultrasound and quantitative angiography used before and after balloon dilation and at 42-day follow-up. The animals were randomly divided into 2 groups, the Batimastat group (n=6) and the vehicle group (n=6). All animals were intraperitoneally injected with either Batimastat or a vehicle immediately after balloon dilation and at 2 weeks and 4 weeks after balloon dilation. Angiographic and echographic late lumen loss in the Batimastat group versus the vehicle group was 0.3+/-0.1 versus 0.8+/-0.1 mm (P=0.01) and 2.2+/-0.5 versus 4.9+/-0.7 mm(2) (P=0.004), respectively. Late media-bounded area loss was used as a measure of remodeling after balloon dilation and was 0.9+/-0.6 mm(2) in the Batimastat group compared with 3.8+/-0.8 mm(2) in the vehicle group (P=0.003, mixed model analysis P=0.01). Neointima formation was 1.3+/-0.3 mm(2) in the Batimastat group and 1.0+/-0.2 mm(2) in the vehicle group (P=0. 542).


CONCLUSIONS
Metalloproteinase inhibition by Batimastat significantly reduced late lumen loss after balloon angioplasty by inhibition of constrictive arterial remodeling, whereas neointima formation was not inhibited by MMP inhibition.
de Smet
B J
BJ
Heart Lung Institute, Utrecht University Hospital, and the Interuniversity Cardiology Institute of The Netherlands, Utrecht, The Netherlands.
de Kleijn
D
D
Hanemaaijer
R
R
Verheijen
J H
JH
Robertus
L
L
van Der Helm
Y J
YJ
Borst
C
C
Post
M J
MJ
D000792:Angiography; D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D001161:Arteriosclerosis / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism / Q000628:therapy*; D007083:Iliac Artery / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D007150:Immunohistochemistry; D008264:Macrophages / Q000473:pathology; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D011184:Postoperative Period; D011480:Protease Inhibitors / Q000627:therapeutic use*; D013552:Swine; D013556:Swine, Miniature; D013876:Thiophenes / Q000097:blood / Q000627:therapeutic use*; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000473:pathology; D018084:Ultrasonography, Interventional
D011480:Protease Inhibitors; D013876:Thiophenes; D010649:Phenylalanine; C080985:batimastat; D008666:Metalloendopeptidases