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

Background-Inhibition of matrix metalloproteinase (MMP) activity after ball oon angioplasty by intraperitoneal injection of batimastat reduces late lum en loss by inhibition of constrictive remodeling. In the present study, we investigated whether the oral MMP inhibitor marimastat inhibits constrictiv e remodeling in favor of neutral or expansive remodeling, Methods and Results-In 26 pigs, balloon dilation was performed in 101 perip heral arteries. Pigs were treated with marimastat or served as controls and were euthanized 42 days after intervention. Intravascular ultrasound was p erformed at all time points. Vessel area (VA) loss was assessed by calculat ing the change in VA at termination relative to after intervention. Arterie s were divided in 3 categories: expansive remodeling (VA loss < -5%), neutr al (-5% <less than or equal to> VA loss less than or equal to +5%), and con strictive remodeling (VA loss > +5%), In the marimastat group, a significan t reduction (53%) of late lumen loss was observed that was fully explained by impaired constrictive remodeling. In the marimastat group, the prevalenc e of constrictive remodeling was reduced (38% versus 75% in the control gro up) 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 contra st to the control group, acute luminal gain in the marimastat group did not correlate with late VA loss. Conclusions-Irrespective of the acute luminal gain by balloon dilation, the oral MMP inhibitor marimastat inhibited constrictive arterial remodeling i n favor of both neutral and expansive remodeling.