Metalloproteinase inhibition reduces constrictive arterial remodeling after balloon angioplasty - A study in the atherosclerotic yucatan micropig

Background-Arterial remodeling after balloon angioplasty has been recognize d as a major determinant of restenosis. Perturbation of collagen metabolism might be important. After balloon injury, matrix metalloproteinase (MMP) e xpression is upregulated. We investigated the effect of Batimastat, a nonsp ecific MMP inhibitor, on late lumen loss, arterial remodeling, and neointim a formation after balloon dilation. Methods and Results-In atherosclerotic iliac arteries of 12 Yucatan micropi gs, balloon dilation was performed, with intravascular ultrasound and quant itative angiography used before and after balloon dilation and at 42-day fo llow-up. The animals were randomly divided into 2 groups, the Batimastat gr oup (n=6) and the vehicle group (n=6). All animals were intraperitoneally i njected with either Batimastat or a vehicle immediately after balloon dilat ion and at 2 weeks and 4 weeks after balloon dilation. Angiographic and ech ographic late lumen loss in the Batimastat group versus the vehicle group w as 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 mea sure of remodeling after balloon dilation and was 0.9+/-0.6 mm(2) in the Ba timastat 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 t he Batimastat group and 1.0+/-0.2 mm(2) in the vehicle group (P=0.542). Conclusions-Metalloproteinase inhibition by Batimastat significantly reduce d late lumen loss after balloon angioplasty by inhibition of constrictive a rterial remodeling, whereas neointima formation was not inhibited by MMP in hibition.