Gene transfer for angiogenesis in coronary artery disease.
Angiogenesis is a promising novel therapeutic strategy to provide new venues for blood flow in patients with severe ischemic heart and peripheral vascular disease, who are not candidates for standard revascularization strategies. We describe the underlying mechanisms involved in physiologic and therapeutic angiogenesis, underscoring the relative importance of vasculogenesis, angiogenesis, and arteriogenesis. We then present the various gene transfer vectors including plasmid, viral, and cell-based vectors, and various delivery modalities. The available preclinical data are presented, followed by a description of preliminary clinical experience, with an emphasis on the preliminary nature of these results, which address safety and not efficacy. Finally, we discuss the promises and pitfalls of clinical angiogenesis and gene transfer studies, stressing the importance of proper design of clinical trials and adequate protection of research subjects.
Laham
R J
RJ
Angiogenesis Research Center, Interventional Cardiology Section, Department of Medicine, Harvard Medical School and Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, Massachusetts 02215, USA. rlaham@bidmc.harvard.edu
Simons
M
M
Sellke
F
F
D003327:Coronary Disease / Q000628:therapy*; D004992:Ethics, Medical; D005544:Forecasting; D018014:Gene Transfer Techniques / Q000639:trends; D005822:Genetic Vectors / Q000627:therapeutic use; D006801:Humans; D018919:Neovascularization, Physiologic / Q000235:genetics; D010344:Patient Advocacy; D012107:Research Design / Q000592:standards; D016896:Treatment Outcome