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Inhibition of interleukin-1beta convertase is associated with decrease of neointimal hyperplasia after coronary
Mariann Gyöngyösi1, Wolfgang Sperker, Csaba Csonka
1Division of Cardiology, 2nd Department of Internal Medicine, University of Vienna Medical Center, Vienna, Austria. mariann.gyongyosi@univie.ac.at
Molecular and Cellular Biochemistry
|September 6, 2003
Summary
Inhibiting IL-1beta convertase with Ac-YVAD-cmk significantly reduced neointimal hyperplasia after coronary stenting in pigs. This treatment decreased inflammation and apoptosis, leading to smaller in-stent volumes and reduced stenosis.
Area of Science:
- Cardiovascular Research
- Inflammation Biology
- Pharmacology
Background:
- Neointimal hyperplasia is a key factor in vascular restenosis after interventions like stenting.
- Inflammation and apoptosis contribute significantly to neointimal development.
- Interleukin-1 beta (IL-1beta) convertase inhibition shows potential for reducing these processes.
Purpose of the Study:
- To evaluate the efficacy of acetyl-tyrosinyl-valyl-alanyl-aspartyl-chloromethyl-ketone (Ac-YVAD-cmk), an irreversible IL-1beta convertase and caspase-1 inhibitor, in reducing neointimal proliferation post-coronary stenting.
- To assess the impact of Ac-YVAD-cmk on inflammation, apoptosis, and vascular remodeling in a porcine model.
Main Methods:
- Porcine coronary arteries were stented, with 8 pigs receiving intracoronary Ac-YVAD-cmk (group 1) and 8 serving as controls (group 2).
- Coronary angiography and 3D intracoronary ultrasound (IVUS) were performed after 4 weeks.
- Neointimal thickness, area, volume, stenosis percentage, apoptotic indices, and IL-1beta levels were quantified.
Main Results:
- Ac-YVAD-cmk treated group showed significantly smaller in-stent intimal volume (27.3 vs. 75.8 mm3) and reduced maximal percentage area stenosis (36.1% vs. 69.0%).
- Maximal neointimal thickness and area were significantly decreased in the treated group (0.63 mm vs. 1.75 mm and 2.14 mm2 vs. 5.03 mm2, respectively).
- Lower apoptotic indices (3.0% vs. 13.4%) and reduced coronary IL-1beta levels (0.254 pg/mg vs. 0.463 pg/mg) were observed in Ac-YVAD-cmk treated pigs.
Conclusions:
- Intracoronary administration of Ac-YVAD-cmk effectively reduces neointimal hyperplasia after coronary stenting.
- The mechanism involves the inhibition of local IL-1beta production and a decrease in neointimal cell apoptosis.
- Ac-YVAD-cmk represents a potential therapeutic strategy for preventing restenosis post-vascular intervention.