Title
Inhibition of interleukin-<tex>$1\beta$</tex> convertase is associated with decrease of neointimal hyperplasia after coronary artery stenting in pigs Inhibition of interleukin-<tex>$1\beta$</tex> convertase is associated with decrease of neointimal hyperplasia after coronary artery stenting in pigs
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Faculty of Medicine and Health Sciences
Publication type
article
Publication
The Hague ,
Subject
Biology
Human medicine
Source (journal)
Molecular and cellular biochemistry. - The Hague
Volume/pages
249(2003) :1-2 , p. 39-43
ISSN
0300-8177
ISI
000184191200006
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Inhibition of IL-1beta convertase has been shown to decrease inflammation and apoptosis, which are features of the neointimal development after vascular interventions. The aim of our study was to reduce neointimal proliferation after stenting of the porcine coronary artery, using the irreversible IL-1beta convertase and caspase-1 inhibitor acetyl-tyrosinyl-valyl-alanyl-aspartyl-chloromethyl-ketone (Ac-YVAD-cmk). Before coronary stent implantation, 8 pigs received an intracoronary infusion of 50 mg Ac-YVAD-cmk into the left coronary artery ( group 1, n = 8), while 8 animals served as untreated controls ( group 2). After 4 weeks, coronary angiography and intracoronary ultrasound (IVUS) with 3D measurements were performed. IVUS revealed a smaller in-stent intimal volume (27.3 +/- 11.6 vs. 75.8 +/- 18.4 mm(3), p < 0.005) and a decreased maximal percentage area stenosis (36.1 +/- 8.5 vs. 69.0 +/- 8.2%, p < 0.001) in group 1 vs. group 2. A smaller maximal neointimal thickness (0.63 +/- 0.28 vs. 1.75 +/- 0.94 mm, p < 0.005) and a decreased maximal neointimal area (2.14 +/- 1.29 vs. 5.03 +/- 1.92 mm(2), p < 0.005), assessed by computerized planimetry, were found in group 1 vs. group 2. Lower apoptotic indices of the neointimal cells were observed in the treated animals (3.0 vs. 13.4% of total intimal cells, p < 0.05). The coronary arterial tissue IL-1β level was significantly decreased in the animals treated with Ac-YVAD-cmk (0.254 +/- 0.162 vs. 0.463 +/- 0.307 pg/mg protein, p < 0.05), and exhibited a positive linear correlation (r = 0.581, p = 0.013) with the in-stent plaque volume. In conclusion, intracoronary administration of Ac-YVAD-cmk before coronary artery stenting results in significantly decreased neointimal hyperplasia due to the inhibition of local IL-1beta production and decreased neointimal apoptosis.
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