Insights into the molecular pathogenesis of atherosclerosis and therapeutic strategies using gene transfer

Citation
Mo. Hiltunen et al., Insights into the molecular pathogenesis of atherosclerosis and therapeutic strategies using gene transfer, VASC MED, 5(1), 2000, pp. 41-48
Citations number
129
Categorie Soggetti
Cardiovascular & Respiratory Systems
Journal title
VASCULAR MEDICINE
ISSN journal
1358863X → ACNP
Volume
5
Issue
1
Year of publication
2000
Pages
41 - 48
Database
ISI
SICI code
1358-863X(200002)5:1<41:IITMPO>2.0.ZU;2-H
Abstract
Gene therapy for the treatment of atherosclerosis and related diseases has shown its potential in animal models and in the first human trials. Gene tr ansfer to the vascular system can be performed both via intravascular and e xtravascular periadventitial routes. Intravascular gene transfer can be don e with several types of catheters under fluoroscopic control. Extravascular gene transfer, on the other hand, provides a well-targeted gene delivery r oute available during vascular surgery. It can be done with direct injectio n or by using perivascular cuffs or surgical collagen sheets. Ex vivo gene delivery via transfected smooth muscle cells or endothelial cells might be useful for the production of secreted therapeutic compounds. Gene transfer to the liver has been used for the treatment of hyperlipidemia. The first c linical trials for the induction of therapeutic angiogenesis in ischemic my ocardium or peripheral muscles with VEGF or FGF gene transfer are under way and preliminary results are promising. VEGF has also been used for the pre vention of postangioplasty restenosis because of its capability to induce e ndothelial repair and production of NO and prostacyclin. However, further b asic research is needed to fully understand the pathophysiological mechanis ms involved in conditions related to atherosclerosis. Also, further develop ment of gene transfer vectors and gene delivery techniques will improve the efficacy and safety of human gene therapy.