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Metalloproteinase inhibition reduces constrictive arterial remodeling after balloon angioplasty: A study in the atherosclerotic Yucatan micropig

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Author: Smet, B.J.G.L. de · Kleijn, D. de · Hanemaaijer, R. · Verheijen, J.H. · Robertus, L. · Helm, Y.J.M. van der · Borst, C. · Post, M.J.
Institution: Gaubius Instituut TNO
Source:Circulation, 25, 101, 2962-2967
Identifier: 235594
Keywords: Angiography · Angioplasty, Balloon · Animals · Arteriosclerosis · Iliac Artery · Immunohistochemistry · Macrophages · Metalloendopeptidases · Phenylalanine · Postoperative Period · Protease Inhibitors · Swine · Swine, Miniature · Thiophenes · Tunica Intima · Ultrasonography, Interventional


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. Methods and 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 mm2 (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 mm2 in the Batimastat group compared with 3.8±0.8 mm2 in the vehicle group (P=0.003, mixed model analysis P=0.01). Neointima formation was 1.3±0.3 mm2 in the Batimastat group and 1.0±0.2 mm2 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. Chemicals/CAS: batimastat, 130370-60-4; Metalloendopeptidases, EC 3.4.24.-; Phenylalanine, 63-91-2; Protease Inhibitors; Thiophenes