The role of c-jun in PDTC-sensitive flow-dependent restenosis after angioplasty and stenting.

Abstract

Restenosis after balloon angioplasty and stenting is exacerbated by low flow. Flow-dependent restenosis after angioplasty but not stenting is prevented by the antioxidant pyrrolidine dithiocarbamate (PDTC). c-jun may play a role in these events as AP-1 activity is both flow and redox sensitive. Carotid arteries of cholesterol fed rabbits underwent stenting or balloon injury in the presence of low or normal flow. c-jun mRNA expression was enhanced by low flow and injury (stent>balloon) and inhibited by the antioxidant PDTC irrespective of the injury type. The effect of locally delivered DZ13 (a DNAzyme specific for c-jun) or scrambled DZ13 (inactive DNAzyme) was assessed by histomorphometry at 28 days. Low flow significantly increased intimal hyperplasia in B and S relative to normal flow (P<0.05). The active DNAzyme DZ13 markedly reduced intimal hyperplasia (P<0.001) and increased lumen size (P<0.05) in balloon-injured but not in stented segments, and abrogated the effect of low flow on restenosis after angioplasty, similar to the morphological effects of PDTC. We conclude that c-jun expression is enhanced by low flow and by injury (stent>balloon) and markedly attenuated by PDTC, and that c-jun is an important mediator of flow-dependent restenosis in balloon-injured but not stented vessels.

• Authors: Melanie Murrell, Levon Khachigian, Michael R Ward
• Journal: Atherosclerosis (Atherosclerosis) Vol. 194 Issue 2 Pg. 364-71 (Oct 2007) ISSN: 1879-1484 [Electronic] Ireland
• PMID: 17194461 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• DNA, Catalytic
• Dz13 DNAzyme
• Proto-Oncogene Proteins c-jun
• Pyrrolidines
• Thiocarbamates
• pyrrolidine dithiocarbamic acid

Topics

• Angioplasty, Balloon (adverse effects)
• Animals
• Antioxidants (pharmacology)
• Blood Flow Velocity (physiology)
• Carotid Artery, Common (physiopathology)
• Carotid Stenosis (physiopathology)
• Coronary Restenosis (physiopathology)
• DNA, Catalytic (pharmacology)
• Diet, Atherogenic
• Disease Models, Animal
• Gene Expression Regulation
• Genes, jun (drug effects)
• Proto-Oncogene Proteins c-jun (drug effects, genetics, metabolism)
• Pyrrolidines (pharmacology)
• Rabbits
• Stents (adverse effects)
• Thiocarbamates (pharmacology)