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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1269.)
© 2001 American Heart Association, Inc.

Vascular Biology

Arterial Elastase Activity After Balloon Angioplasty and Effects of Elafin, an Elastase Inhibitor

Alan W. Barolet; Nafiseh Nili; Asim Cheema; Ranga Robinson; Madhu K. Natarajan; Stacy O’Blenes; Jing Li; Mohammad R. Eskandarian; John Sparkes; Marlene Rabinovitch; Bradley H. Strauss

From the Terrence Donnelly Heart Centre (A.W.B., N.N., A.C., R.R., M.K.N., J.L., M.R.E., J.S., B.H.S.), Division of Cardiology, St. Michael’s Hospital; the Division of Cardiovascular Research, Research Institute (S.O., M.R.), The Hospital for Sick Children; Division of Cardiology, Mount Sinai Hospital (A.W.B.), and the Departments of Medicine, Pediatrics and Pathology, University of Toronto, Toronto, Canada.

Correspondence to Dr Bradley H. Strauss, Terrence Donnelly Heart Centre, St. Michael’s Hospital, 30 Bond St, Toronto, Ontario, Canada M5B 1W8. E-mail straussb{at}smh.toronto.on.ca

Abstract—— Increased proteolytic activity may be a factor in intimal hyperplasia after balloon angioplasty (BA). The objectives of this study were to assess elastase activity after BA in a rabbit arterial double-injury model and the effects 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 significantly inhibited in vitro by elafin and phenylmethylsulfonyl fluoride, selective inhibitors of serine elastases. A second group of animals was transfected after BA with a plasmid containing the cDNA for either elafin or a control (chloramphenicol acetyltransferase, CAT) construct by using a hemagglutinating virus of Japan–liposome transfection technique. Arterial segments were obtained at 48 hours, 1 week, and 4 weeks to assess transgene expression, arterial wall elastase activity, and intimal cross-sectional area, respectively. Elafin transgene expression was evident at 48 hours and resulted in a significant (80%) inhibition of elastase activity compared with chloramphenicol acetyltransferase–transfected arteries. There was a 43% reduction in intimal cross-sectional area in elafin-transfected arteries (0.28±0.22 versus 0.16±0.07 mm² for CAT-transfected versus elafin-transfected arteries, respectively; P<0.05). These data suggest that an early increase in serine elastase activity after BA contributes to intimal hyperplasia. Serine elastase inhibition may be a potential therapeutic approach to inhibit intimal hyperplasia.

Key Words: angioplasty • restenosis • elastase • elafin

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