Circulation. 1998;97:1108-1110
(Circulation. 1998;97:1108-1110.)
© 1998 American Heart Association, Inc.
Therapeutic Angiogenesis in Ischemic Limbs
Judah Folkman, MD
From Children's Hospital and Harvard Medical School, Boston, Mass.
Correspondence to Judah Folkman, MD, Julia Dyckman Professor of Pediatric Surgery and Professor of Cell Biology, Children's Hospital and Harvard Medical School, Hunnewell 103, 300 Longwood Ave, Boston, MA 02115.
Key Words: Editorials • angiogenesis • endothelium • hypoxia • ischemia
In this issue of
Circulation, Baumgartner et al1 ). The plasmid DNA was injected
directly into the muscle of ischemic limbs. Anatomic and
functional efficacy was demonstrated by increased serum levels of VEGF,
improved hemodynamic measurements and angiographic
evaluation, reduced pain, increased healing of ischemic ulcers,
limb salvage, and immunohistochemical evidence of proliferating
endothelial cells in tissue specimens. The authors
emphasize that this is the first medical therapy to achieve an increase
in limb perfusion that is equivalent to or greater than successful
surgical or percutaneous intervention.
Direct intramuscular gene transfer of plasmid DNA appears to
effectively stimulate collateral vessel growth, despite the lower
transfection efficiency that is usually associated with gene therapy in
the absence of a viral vector. This result has implications for other
clinical trials of gene therapy that use intramuscular naked DNA. The
fact that Isner's group could prepare the plasmid for human use in a
university medical center laboratory dedicated to this purpose reveals
why gene therapy has moved so rapidly from the laboratory to the
clinic, in contrast to protein therapy, which requires expensive
manufacturing facilities and years of scale-up effort.
Although the plasmid was injected into muscle of the
ischemic limb, VEGF levels were apparently elevated in the
whole circulation, as evidenced by transient peaks of VEGF in the serum
and by edema of the ischemic limb and in some patients, in the
opposite limb. The increased collateral vessels, however, are localized
to the ischemic limb and do not develop in other . . . [Full Text of this Article]
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