Adenoviral activin A expression prevents vein graft intimal hyperplasia in a rat model.
Autologus vein grafts are used for coronary artery and infra-inguinal bypass procedures. Although initially successful, long-term patency rates are limited by lumen occlusion due to neointima formation by smooth muscle cell hyperplasia. Gene therapy to prevent this smooth muscle cell proliferation has been studied extensively with limited success. Activin A, a member of the transforming growth factor-beta super family, promotes the contractile phenotype of smooth muscle cells. Maintaining the contractile phenotype could be a novel strategy to prevent intimal hyperplasia. In an epigastric vein-to-common femoral artery interposition grafts rat model, activin A over-expression resulted in a significant decrease in intimal cross-sectional area and percentage stenosis as compared to the control group. BrdU staining identified lower proliferation rates of the smooth muscle cells in the group treated with activin A. We report for the first time evidence that activin A can diminish vein graft failure in a rat model supporting a novel strategy to prevent intimal hyperplasia.
Department of Medical Microbiology and Maastricht Infection Center, University Hospital Maastricht, Maastricht, The Netherlands. Geoffrey_kloppenburg@hotmail.com
Geoffrey T L
GT
Kloppenburg
Gert E
GE
Grauls
Cathrien A
CA
Bruggeman
Frank R
FR
Stassen
D000009:Abdominal Muscles / Q000098:blood supply; D000199:Actins; D028341:Activins / Q000235:genetics*; D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation; D003251:Constriction, Pathologic; D005263:Femoral Artery / Q000601:surgery; D015316:Genetic Therapy; D005822:Genetic Vectors; D006083:Graft Occlusion, Vascular / Q000209:etiology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D006965:Hyperplasia; D028322:Inhibin-beta Subunits / Q000235:genetics*; D008297:Male; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D014656:Vascular Surgical Procedures / Q000009:adverse effects*; D014680:Veins / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*
D000199:Actins; D028341:Activins; D001973:Bromodeoxyuridine; D028322:Inhibin-beta Subunits; C422405:activin A; C103008:inhibin beta A subunit; C498862:Acta2 protein, rat