Gene therapy in vascular medicine: recent advances and future perspectives.
Gene therapy is emerging as a potential strategy for the treatment of cardiovascular diseases, such as restenosis after angioplasty, vascular bypass graft occlusion, and transplant coronary vasculopathy, for which no known effective therapy exists. The first human trial in cardiovascular disease was started in 1994 to treat peripheral vascular disease using vascular endothelial growth factor. In addition, therapeutic angiogenesis using the vascular endothelial growth factor gene was applied in the treatment of ischemic heart disease. The results from these clinical trials seem to exceed expectation. Improvement of clinical symptoms in peripheral arterial disease and ischemic heart disease has been reported. At least five different potent angiogenic growth factors have been tested in clinical trials to treat peripheral arterial disease or ischemic heart disease. In addition, another strategy for combating disease processes, to target the transcriptional process, has been tested in a human trial. Transfection of cis-element double-stranded oligodeoxynucleotides is an especially powerful tool in a new class of antigen strategies for gene therapy. Transfection of double-stranded oligodeoxynucleotides corresponding to the cis sequence will result in the attenuation of the authentic cis-trans interaction, leading to the removal of trans-factors from the endogenous cis-elements, with subsequent modulation of gene expression. Genetically modified vein grafts transfected with a decoy against E2F, an essential transcription factor in cell cycle progression, revealed apparent long-term potency in human patients. This review focuses on the future potential of gene therapy for the treatment of cardiovascular disease.
Morishita
R
R
Division of Gene Therapy Science, Graduate School of Medicine, Osaka University Medical School, Suita, Osaka 565-0871, Japan. morishit@geriat.med.osaka-u.ac.jp
Aoki
M
M
Kaneda
Y
Y
Ogihara
T
T
D017130:Angioplasty; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000628:therapy*; D002986:Clinical Trials as Topic; D023903:Coronary Restenosis / Q000235:genetics / Q000628:therapy; D016228:Endothelial Growth Factors / Q000627:therapeutic use; D005095:Exoribonucleases / Q000627:therapeutic use*; D015316:Genetic Therapy / Q000639:trends*; D006801:Humans; D008222:Lymphokines / Q000627:therapeutic use; D018919:Neovascularization, Physiologic; D016491:Peripheral Vascular Diseases / Q000235:genetics* / Q000628:therapy; D014158:Transcription, Genetic; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014680:Veins / Q000637:transplantation
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D005095:Exoribonucleases; C065486:oligonucleotidase