EXTRACELLULAR-MATRIX COLLAGEN-SYNTHESIS AND DEGRADATION FOLLOWING CORONARY BALLOON ANGIOPLASTY

Percutaneous transluminal coronary angioplasty is associated with inti mal hyperplasia and extracellular matrix deposition of collagen, leadi ng to restenosis in a significant number of cases. The purpose of the present study was to determine the effects of balloon angioplasty on e xtracellular matrix collagen content and collagenase activity in a por cine coronary artery restenosis model 6 weeks following balloon injury . We tested the hypothesis that in balloon-injured arteries the neoint imal extracellular matrix was characterized by increased collagen cont ent and decreased metalloproteinase activity relative to non-injured a rteries. Male miniswine maintained on a high cholesterol diet underwen t cardiac catheterization and double balloon injury to the right and l eft circumflex coronary arteries. The coronary arteries were either pr essure-perfusion-fixed and prepared for histological examination, or d issected free of adventitia for further collagen and matrix metallopro teinase studies. Collagen synthesis in balloon-injured coronary arteri es was compared to non-injured arteries using Northern blot analysis a nd histochemical stains. Comparative studies on differences between ba lloon-injured and non-balloon-injured arterial matrix metalloproteinas e activity were done using zymography. Balloon angioplasty arterial in jury resulted in a significant increase in type I collagen mRNA expres sion, with increased collagen deposition in the extracellular matrix. In contrast, matrix metalloproteinase activity was markedly decreased. The results suggest that the increased neointimal extracellular matri x observed late in the injury response may be due to not only increase d collagen synthesis, but also reduced degradation. The failure to ach ieve a balance between the synthesis and degradation of extracellular matrix collagen could serve as an important mechanism responsible for restenosis. (C) 1996 Academic Press Limited