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

AI Virtanen Institute, University of Kuopio, Kuopio, Finland

Mikko P Turunen

AI Virtanen Institute, University of Kuopio, Kuopio, Finland

Marja Laitinen

AI Virtanen Institute, University of Kuopio, Kuopio, Finland, Department of Medicine, University of Kuopio, Kuopio, Finland

Seppo Ylä-Herttuala

AI Virtanen Institute, University of Kuopio, Kuopio, Finland, Department of Medicine, University of Kuopio, Kuopio, Finland, Gene Therapy Unit, University of Kuopio, Kuopio, Finland

Gene therapy for the treatment of atherosclerosis and related diseases has shown its potential in animal models and in the first human trials. Gene transfer to the vascular system can be performed both via intravascular and extravascular periadventitial routes. Intravascular gene transfer can be done with several types of catheters under fluoroscopic control. Extra-vascular gene transfer, on the other hand, provides a well-targeted gene delivery route available during vascular surgery. It can be done with direct injection 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 clinical trials for the induction of therapeutic angiogenesis in ischemic myocardium or peripheral muscles with VEGF or FGF gene transfer are under way and preliminary results are promising. VEGF has also been used for the prevention of postangioplasty restenosis because of its capability to induce endothelial repair and production of NO and prostacyclin. However, further basic research is needed to fully understand the pathophysiological mechanisms involved in conditions related to atherosclerosis. Also, further development of gene transfer vectors and gene delivery techniques will improve the efficacy and safety of human gene therapy.

Key Words: atherogenesis • gene transfer • review

Vascular Medicine, Vol. 5, No. 1, 41-48 (2000)
DOI: 10.1177/1358836X0000500107


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