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Oral matrix metalloproteinase inhibition and arterial remodeling after balloon dilation: An intravascular ultrasound study in the pig

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Author: Sierevogel, M.J. · Pasterkamp, G. · Velema, E. · Jaegere, · Smet, · Verheijen, J.H. · Kleijn, · Borst, C.
Institution: TNO Preventie en Gezondheid
Source:Circulation, 2, 103, 302-307
Identifier: 235955
doi: doi:/10.1161/01.CIR.103.2.302
Keywords: Health · Angioplasty · Metalloproteinases · Remodeling · Stenosis · Ultrasonics · Administration, Oral · Animals · Arteries · Balloon Dilatation · Enzyme Inhibitors · Hydroxamic Acids · Hyperplasia · Matrix Metalloproteinases · Swine · Tunica Intima · Ultrasonography, Interventional


Background - Inhibition of matrix metalloproteinase (MMP) activity after balloon angioplasty by intraperitoneal injection of batimastat reduces late lumen loss by inhibition of constrictive remodeling. In the present study, we investigated whether the oral MMP inhibitor marimastat inhibits constrictive remodeling in favor of neutral or expansive remodeling. Methods and Results - In 26 pigs, balloon dilation was performed in 101 peripheral arteries. Pigs were treated with marimastat or served as controls and were euthanized 42 days after intervention. Intravascular ultrasound was performed at all time points, Vessel area (VA) loss was assessed by calculating the change in VA at termination relative to after intervention. Arteries were divided in 3 categories: expansive remodeling (VA loss < -5%), neutral (-5% ≤ VA loss ≤ +5%), and constrictive remodeling (VA loss > +5%). In the marimastat group, a significant reduction (53%) of late lumen loss was observed that was fully explained by impaired constrictive remodeling. In the marimastat group, the prevalence of constrictive remodeling was reduced (38% versus 75% in the control group) in favor of not only neutral but also expansive remodeling (21% and 42% versus 4% and 21% in the control group, respectively, P<0.01). In contrast to the control group, acute luminal gain in the marimastat group did not correlate with late VA loss. Canclusions - Irrespective of the acute luminal gain by balloon dilation, the oral MMP inhibitor marimastat inhibited constrictive arterial remodeling in favor of both neutral and expansive remodeling.