Reduction of Transplant Vasculopathy by Intraoperative Nucleic Acid-based Therapy in a Mouse Aortic Allograft Model.
Animals
Aorta
/ metabolism
Aortic Diseases
/ genetics
Disease Models, Animal
Female
Fibrosis
Graft Survival
Hyperplasia
Macrophages
/ metabolism
Matrix Metalloproteinases
/ metabolism
Mice, Inbred C57BL
Mice, Inbred DBA
Neointima
Oligodeoxyribonucleotides
/ genetics
Time Factors
Transcription Factor AP-1
/ genetics
Vascular Remodeling
Journal
The Thoracic and cardiovascular surgeon
ISSN: 1439-1902
Titre abrégé: Thorac Cardiovasc Surg
Pays: Germany
ID NLM: 7903387
Informations de publication
Date de publication:
Sep 2019
Sep 2019
Historique:
pubmed:
24
10
2018
medline:
18
12
2019
entrez:
24
10
2018
Statut:
ppublish
Résumé
Transplant vasculopathy (TV) is the main limiting factor for long-term graft survival characterized by fibrosis, myofibroblast, and smooth muscle cell (SMC) proliferation. Decoy oligodeoxynucleotide (dODN) against the transcription factor activator protein-1 (AP-1) might interfere with the expression of AV-related genes that govern neointima formation. Aortic allografts from DBA/2 mice were incubated with control buffer, consensus, or mutated control AP-1 dODN and were transplanted into the infrarenal aorta of C57BL/6 mice. Cyclosporine A (10 mg/kg body weight [BW]) was administered daily. Explantation and histomorphometric and immunohistochemical evaluation was performed after 30 days. Matrix metalloproteinase (MMP) activity was visualized by gelatin in situ zymography. Intima-to-media (I/M) ratio and neointima formation were significantly reduced in the consensus AP-1 dODN treatment group by 37% ( Intraoperative AP-1dODN utilization might be a strategy to preserve graft function after transplantation.
Sections du résumé
BACKGROUND
BACKGROUND
Transplant vasculopathy (TV) is the main limiting factor for long-term graft survival characterized by fibrosis, myofibroblast, and smooth muscle cell (SMC) proliferation. Decoy oligodeoxynucleotide (dODN) against the transcription factor activator protein-1 (AP-1) might interfere with the expression of AV-related genes that govern neointima formation.
METHODS
METHODS
Aortic allografts from DBA/2 mice were incubated with control buffer, consensus, or mutated control AP-1 dODN and were transplanted into the infrarenal aorta of C57BL/6 mice. Cyclosporine A (10 mg/kg body weight [BW]) was administered daily. Explantation and histomorphometric and immunohistochemical evaluation was performed after 30 days. Matrix metalloproteinase (MMP) activity was visualized by gelatin in situ zymography.
RESULTS
RESULTS
Intima-to-media (I/M) ratio and neointima formation were significantly reduced in the consensus AP-1 dODN treatment group by 37% (
CONCLUSION
CONCLUSIONS
Intraoperative AP-1dODN utilization might be a strategy to preserve graft function after transplantation.
Identifiants
pubmed: 30352477
doi: 10.1055/s-0038-1673633
doi:
Substances chimiques
Oligodeoxyribonucleotides
0
Transcription Factor AP-1
0
Matrix Metalloproteinases
EC 3.4.24.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
503-512Informations de copyright
Georg Thieme Verlag KG Stuttgart · New York.
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest.