Genetic interventions for vein bypass graft disease: a review.
The failure of vein bypass grafting in the coronary or lower extremity circulation is a common clinical occurrence that incurs significant morbidity, mortality, and cost. Vein grafts are uniquely amenable to intraoperative genetic modification because of the ability to manipulate the tissue ex vivo with controlled conditions. Although the pathophysiology of vein graft failure is incompletely understood, numerous relevant molecular targets have been elucidated. Interventions designed to influence cell proliferation, thrombosis, inflammation, and matrix remodeling at the genetic level have been described, and many have been tested in animal models. Both gene delivery and gene blockade strategies have been investigated, with the latter now reaching the stage of advanced clinical trials. This review describes the basic and translational science of genetic interventions for vein graft disease and the current state of application in the clinic.
Conte
Michael S
MS
Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA.
Mann
Michael J
MJ
Simosa
Hector F
HF
Rhynhart
Kurt K
KK
Mulligan
Richard C
RC
D000818:Animals; D001807:Blood Vessel Prosthesis; D002455:Cell Division; D015316:Genetic Therapy; D006083:Graft Occlusion, Vascular / Q000628:therapy*; D006801:Humans; D007249:Inflammation / Q000628:therapy; D007866:Leg / Q000098:blood supply; D018384:Oxidative Stress; D015427:Reperfusion Injury / Q000628:therapy; D013927:Thrombosis / Q000628:therapy