Decoy oligodeoxynucleotide againstactivator protein-1 reducesneointimal proliferation after coronaryangioplasty in hypercholesterolemic minipigs
Arnd B. Buchwald, MD*,*,
Andreas H. Wagner, PhD ,
Christian Webel* and
Markus Hecker, PhD
* Departments of Cardiology and Pneumology, University of Goettingen, Goettingen, Germany
Department of Cardiovascular Physiology, University of Goettingen, Goettingen, Germany
View larger version (73K):
[in a new window]
|
Figure 1 Immunohistochemical detection of endothelin-1 (ET-1) in the coronary arteries of the same animal treated with (a) vehicle or (b) the activator protein-1 (AP-1) consensus decoy oligodeoxynucleotide (dODN) 48 h after percutaneous transluminal coronary angioplasty. Positive immunoreactivity for ET-1, both in the periluminal cell layers and in the media, is markedly reduced in the AP-1 consensus dODN-treated artery (original x400, before 00% reduction). The results shown are representative of those obtained with four different animals.
|
|
View larger version (40K):
[in a new window]
|
Figure 2 (a) The effects of pretreatment (1 h) with activator protein-1 (AP-1) consensus (AP-1 cons) or AP-1 mutant (AP-1 mut) decoy oligodeoxynucleotide (dODN) (10 µmol/l each) on phorbol dibutyrate (1 µmol/l)-induced nuclear translocation of AP-1 in endothelium-intact segments of the porcine left anterior descending coronary artery from the same animal. The segments were incubated in Waymouth medium containing 10% fetal bovine serum for 1 h at 37°C, followed by electrophoretic mobility shift analysis. The results shown are representative of at least two further experiments with segments from different animals. (b) In vivo treatment of porcine coronary arteries from the same animal, with AP-1 consensus dODN resulting in a diminished nuclear translocation of AP-1 relative to the buffer control 48 h after percutaneous transluminal coronary angioplasty (upper box), although nuclear translocation of CCAAT/enhancer binding protein (C/EBP)ß and - was not affected. The results shown are representative of those obtained with four different animals. Identification of the C/EBP family members was done by supershift analysis (10).
|
|
View larger version (51K):
[in a new window]
|
Figure 3 The proliferative vessel wall response four weeks after stent angioplasty in three coronary arteries from the same animal infused with vehicle (a), activator protein-1 (AP-1) consensus decoy oligodeoxynucleotide (dODN) (b) or AP-1 mutant dODN (c). Extensive proliferation in (a) and (c) is markedly reduced in the AP-1 consensus dODN-infused artery (elastica–van Gieson staining, original x40, before 00% reduction).
|
|
View larger version (22K):
[in a new window]
|
Figure 4 A comparison of the effects of activator protein-1 (AP-1) consensus (AP-1 cons) decoy oligodeoxynucleotide (dODN), AP-1 mutant (AP-1 mut) dODN and buffer control on neointimal area (a) and lumen area (b), expressed as the percentage of the in-stent area four weeks after percutaneous transluminal coronary angioplasty. *p < 0.05 vs. buffer control. p < 0.05 vs. AP-1 mutant dODN.
|
|
View larger version (21K):
[in a new window]
|
Figure 5 (a) A comparison of the effects of activator protein-1 (AP-1) consensus (AP-1 cons) and AP-1 mutant (AP-1 mut) decoy oligodeoxynucleotide (dODN) on neointimal area eight weeks after percutaneous transluminal coronary angioplasty (PTCA). (b) A lack of effect of C/EBP consensus (C/EBP cons) and C/EBP mutant (C/EBP mut) dODN on neointimal area four weeks after PTCA (see Fig. 4a for comparison).
|
|
|
