Arterial elastase activity after balloon angioplasty and effects of elafin, an elastase inhibitor

Increased proteolytic activity may be a factor in intimal hyperplasia after balloon angioplasty (BA). The objectives of this study were to assess elas tase activity after BA in a rabbit arterial double-injury model and the eff ects of elastase inhibition. Elastase activity increased immediately after BA, reached an 8-fold peak at 1 week, and declined to baseline levels by 4 weeks. Elastin zymography showed that the elastase activity was associated predominantly with a molecular mass of 25 kDa. Elastase activity was signif icantly inhibited in vitro by elafin and phenymethylsulfonyl fluoride, sele ctive inhibitors of serine elastases. A second group of animals was transfe cted after BA with a plasmid containing the cDNA for either elafin or a con trol (chloramphenicol acetyltransferase, CAT) construct by using a hemagglu tinating virus of Japan-liposome transfection technique. Arterial segments were obtained at 48 hours, 1 week, and 4 weeks to assess transgene expressi on, arterial wall elastase activity, and intimal. cross-sectional area, res pectively. Elafin transgene expression was evident at 48 hours and resulted in a significant (80%) inhibition of elastase activity compared with chlor amphenicol acetyltransferase-transfected arteries. There was a 43% reductio n in intimal cross-sectional area in elafin-transfected arteries (0.28 +/-0 .22 versus 0.16 +/-0.07 mm(2) for CAT-transfected versus elafin-transfected arteries, respectively; P <0.05). These data suggest that an early increas e in serine elastase activity after BA contributes to intimal hyperplasia. Serine elastase inhibition may be a potential therapeutic approach to inhib it intimal hyperplasia.