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All-trans-retinoic acid decreases cell proliferation and increases apoptosis in an animal model of vein bypass grafting. Surgery 2000 Aug;128(2):178-84



Pubmed ID




Scopus ID

2-s2.0-0033863885   16 Citations


BACKGROUND: We have previously demonstrated a decrease in intimal hyperplasia in vein bypass grafts from animals treated with all-trans-retinoic acid (atRA). The purpose of this study was to examine the effect of atRA on proliferation and apoptosis rates in healing vein bypass grafts.

METHODS: Interposition jugular vein bypass grafts were placed in the carotid artery of 30 New Zealand white rabbits. Animals received either atRA (10 mg/kg/d) or vehicle (corn oil) for a period of 2 weeks. Animals were killed at 3, 7, or 28 days after graft placement after having received 3 doses of 5-bromo-2'-┬┐Deoxyuridine (BRDU, 35 Mg/KG). Animals Were Perfusion Fixed, And Vein Grafts Were Prepared For Immunohistochemistry By Using Antibodies To Brdu, Proliferating Cell Nuclear Antigen, And Bcl-XL. Apoptosis Was Measured By Using The Tunel Assay. Histologic Sections Were Analyzed By A Pathologist Blinded To The Study, And An Index Of Positively Stained Cells Was Generated For Each Layer Of The Vein Graft Wall.

RESULTS: All-trans-retinoic acid reduced the proliferation index in the neointima of vein grafts during the first week after surgery. Apoptotic rates were higher in the intima of vein grafts from animals treated with atRA, which could not be explained by changes in bcl-xl expression. No differences were noted in the media or adventitia between the groups.

CONCLUSIONS: atRA decreased cell proliferation and increased apoptosis in the intima of healing vein bypass grafts. These effects contribute to decreased intimal hyperplasia, which has been previously noted.

Author List

Leville CD, Osipov VO, Jean-Claude JM, Seabrook GR, Towne JB, Cambria RA


Gary R. Seabrook MD Chief, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Anastomosis, Surgical
Carotid Arteries
Cell Division
Cell Nucleus
In Situ Nick-End Labeling
Jugular Veins
Muscle, Smooth, Vascular
Proliferating Cell Nuclear Antigen
Proto-Oncogene Proteins c-bcl-2
Transplantation, Autologous
Tunica Intima
Vascular Surgical Procedures
bcl-X Protein
jenkins-FCD Prod-468 69a93cef3257f26b866d455c1d2b2d0f28382f14