Here we show that the genetic loss of Akt1, but not Akt2, in mice results in defective ischemia and VEGF-induced angiogenesis as well as severe peripheral vascular disease.
The first human trial in gene therapy for cardiovascular disease was started at 1994 to treat peripheral vascular disease using vascular endothelial growth factor (VEGF).
The first human trial in cardiovascular disease was started in 1994 to treat peripheral vascular disease using vascular endothelial growth factor (VEGF).
We sought to investigate the safety and efficacy of intramuscular gene therapy with vascular endothelial growth factor (VEGF) in patients with chronic critical leg ischemia.Gene transfer was performed in 24 limbs of 21 patients with rest pain, some of whom also had nonhealing ischemic ulcers (n = 16) due to occlusive peripheral arterial disease.
Regional angiogenesis with vascular endothelial growth factor in peripheral arterial disease: a phase II randomized, double-blind, controlled study of adenoviral delivery of vascular endothelial growth factor 121 in patients with disabling intermittent claudication.
We administered: 1) Ad(GV)CFTR.10, a vector carrying the normal human CFTR cDNA (3 x 10(7) to 2 x 10(10) particle units (pu)) to airways of individuals with cystic fibrosis (CF); 2) Ad(GV)VEGF121.10, a vector carrying the normal human vascular endothelial growth factor (VEGF)121 cDNA, to the myocardium (4 x 10(8) to 4 x 10(10) pu) of individuals with coronary artery disease (CAD) and to lower extremity muscles (4 x 10(8) to 4 x 10(9.5) pu) of individuals with peripheral vascular disease (PVD); and 3) Ad(GV)CD.10, a vector carrying the Escherichia coli cytosine deaminase gene to skin (7 x 10(7) to 7 x 10(9) pu) and airways (7 x 10(8) to 7 x 10(10) pu) of normal individuals and to liver metastasis (4 x 10(8) to 4 x 10(9) pu) of individuals with colon carcinoma.
The first human trial in cardiovascular disease started in 1994 treating peripheral vascular disease with vascular endothelial growth factor (VEGF) and since then, many different potent angiogenic growth factors have been tested in clinical trials for the treatment of peripheral arterial disease.
Adenoviral gene transfer of VEGF(121.10) appears to modulate endothelial function and lower-extremity flow reserve in patients with peripheral arterial disease.
The impressive progress being made toward the use of VEGF gene therapy for effective therapeutic angiogenesis in ischemic peripheral vascular disease is truly welcome news for clinicians faced with the task of providing care for those patients suffering from lower-limb vascular insufficiency.