Inhibition of intravascular thrombosis and vascular smooth muscle cell proliferation by gene therapy.
Intravascular thrombosis, smooth muscle cell proliferation and matrix production lead to arterial luminal narrowing and reduction of blood flow to various organs. Alteration of gene expression of the arterial wall cells to inhibit thrombosis and smooth muscle activation is emerging as a new and exciting therapeutic modality for cardiovascular pathology. We have used genetically modified endothelial cells to seed endovascular prostheses and tested cell adhesion to the prostheses both in vitro and in vivo. We also used two catheter-based systems to deliver genes directly to the arterial wall cells in vivo employing retroviral and adenoviral vectors. With efficient vectors for gene transfer and high level expression of proteins by the transduced cells, gene therapy will serve as a major therapy for post-angioplasty restenosis, unstable angina pectoris and vascular grafts stenosis.
Flugelman
M Y
MY
Department of Cardiology, Lady Davis Carmel Medical Center, Haifa, Israel.
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology / Q000628:therapy; D002404:Catheterization / Q000295:instrumentation / Q000379:methods; D002448:Cell Adhesion; D002478:Cells, Cultured / Q000637:transplantation; D003327:Coronary Disease / Q000378:metabolism / Q000473:pathology; D003331:Coronary Vessels / Q000737:chemistry; D004730:Endothelium, Vascular / Q000166:cytology; D005346:Fibroblast Growth Factors / Q000032:analysis; D017930:Genes, Reporter; D005818:Genetic Engineering; D015316:Genetic Therapy / Q000295:instrumentation / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000096:biosynthesis; D012190:Retroviridae / Q000235:genetics; D012756:Sheep; D015607:Stents; D013927:Thrombosis / Q000517:prevention & control*; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000627:therapeutic use
D011994:Recombinant Proteins; D005346:Fibroblast Growth Factors; D010959:Tissue Plasminogen Activator