The emerging clinical potential of cardiovascular gene therapy.
Despite considerable progress, pharmacological therapies have not provided a complete solution for common cardiovascular problems, including recurrent thrombosis, restenosis, and vein graft deterioration. Optimal drug dosage, reproducing plasma concentrations achieved in animal studies establishing proof-of-principle, would often be too toxic to administer, especially when given over prolonged periods of time. Local gene therapy aims at overexpressing proteins that: (1) regulate the cell cycle of VSMC; (2) inhibit VSMC migration; (3) endow the endothelium with its vasoprotective properties; and (4) stimulate growth of endothelium and angiogenesis. Alternatively, some approaches tend to suppress gene expression of proteins believed to promote VSMC proliferation and migration. In sharp contrast to drug treatments, local gene therapy limits expression of the beneficial agent to the injured vascular site, and there, it can extend the presence of this agent to weeks and, with some gene vectors, to many months. The clinical potential of this approach has led to the initiation of trials that currently evaluate gene therapy approaches to the attenuation of peripheral and myocardial ischaemia and the prevention of vein graft disease.
Zoldhelyi
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P
Gene Therapy Research Laboratory, The University of Texas Medical School at Houston, USA. zoldhely@901.com
Eichstaedt
H
H
Jax
T
T
McNatt
J M
JM
Chen
Z Q
ZQ
Shelat
H S
HS
Rose
H
H
Willerson
J T
JT
D000818:Animals; D002986:Clinical Trials as Topic; D003327:Coronary Disease / Q000628:therapy*; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D008297:Male; D011379:Prognosis; D016896:Treatment Outcome