Prevention of coronary in-stent restenosis and vein graft failure: does vascular gene therapy have a role?
Coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI), including stent insertion, are established therapies in both acute coronary syndromes (ACS) and symptomatic chronic coronary artery disease refractory to pharmacological therapy. These continually advancing treatments remain limited by failure of conduit grafts in CABG and by restenosis or thrombosis of stented vessel segments in PCI caused by neointimal hyperplasia, impaired endothelialisation and accelerated atherosclerosis. While pharmacological and technological advancements have improved patient outcomes following both procedures, when grafts or stents fail these result in significant health burdens. In this review we discuss the pathophysiology of vein graft disease and in-stent restenosis, gene therapy vector development and design, and translation from pre-clinical animal models through human clinical trials. We identify the key issues that are currently preventing vascular gene therapy from interfacing with clinical use and introduce the areas of research attempting to overcome these.
British Heart Foundation Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
Keith E
KE
Robertson
Robert A
RA
McDonald
Keith G
KG
Oldroyd
Stuart A
SA
Nicklin
Andrew H
AH
Baker
D000256:Adenoviridae / Q000235:genetics; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000818:Animals; D002986:Clinical Trials as Topic; D023903:Coronary Restenosis / Q000517:prevention & control*; D000229:Dependovirus / Q000235:genetics; D004730:Endothelium, Vascular / Q000502:physiology; D015316:Genetic Therapy; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D058426:Neointima / Q000473:pathology; D012190:Retroviridae / Q000235:genetics; D015607:Stents / Q000009:adverse effects*; D014680:Veins / Q000637:transplantation*