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
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.