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 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 mm(2) 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.
Barolet
A W
AW
Terrence Donnelly Heart Centre, Division of Cardiology, St. Michael's Hospital, Toronto, Ontario, Canada M5B 1W8.
Nili
N
N
Cheema
A
A
Robinson
R
R
Natarajan
M K
MK
O'Blenes
S
S
Li
J
J
Eskandarian
M R
MR
Sparkes
J
J
Rabinovitch
M
M
Strauss
B H
BH
D000800:Angioplasty, Balloon; D000818:Animals; D001158:Arteries / Q000201:enzymology* / Q000473:pathology; D001161:Arteriosclerosis / Q000201:enzymology / Q000473:pathology* / Q000628:therapy*; D002339:Carotid Arteries; D018076:DNA, Complementary; D004591:Electrophoresis, Polyacrylamide Gel; D006965:Hyperplasia; D007083:Iliac Artery; D007150:Immunohistochemistry; D008081:Liposomes; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000201:enzymology; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D010957:Plasmids; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000235:genetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D018108:Respirovirus; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D014162:Transfection; D019076:Transgenes; D017539:Tunica Intima / Q000201:enzymology* / Q000473:pathology*
D018076:DNA, Complementary; D008081:Liposomes; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D012333:RNA, Messenger; D015842:Serine Proteinase Inhibitors; D010196:Pancreatic Elastase