Abstract
Exogenous vascular endothelial growth factor (VEGF) improves tissue perfusion in large animals and humans with chronic myocardial ischemia. Because tissue perfusion is mainly dependent on the arteriolar tree, we hypothesized that the neovascularizing effect of VEGF should include arteriogenesis, an effect not as yet described in large mammalian models of myocardial ischemia. In the present study we investigated the effect of intramyocardial plasmid-mediated human VEGF165 gene transfer (pVEGF165) on the proliferation of vessels with smooth muscle in a pig model of myocardial ischemia. In addition, we assessed the effect of treatment on capillary growth, myocardial perfusion, myocardial function and collateralization. Three weeks after positioning of an Ameroid constrictor (Research Instruments SW, Escondido, CA) in the left circumflex artery, pigs underwent basal perfusion (single-photon emission computed tomography [SPECT] with 99mTc-sestamibi) and regional function (echocardiography) studies at rest and under dobutamine stress, and were then randomly assigned to receive transepicardial injection of pVEGF165 3.8 mg (n = 8) or placebo (empty plasmid, n = 8). All experimental steps and data analysis were clone in a blinded fashion. Five weeks later, pVEGF165-treated pigs showed a significantly higher density of small (8-50 μm in diameter) vessels with smooth muscle, higher density of capillaries, and improved myocardial perfusion. These results indicate an arteriogenic effect of VEGF in a large mammalian model of myocardial ischemia and encourage the use of VEGF to promote arteriolar growth in patients with severe coronary artery disease.
| Original language | English |
|---|---|
| Pages (from-to) | 1307-1318 |
| Number of pages | 12 |
| Journal | Human Gene Therapy |
| Volume | 14 |
| Issue number | 14 |
| DOIs | |
| Publication status | Published - Sep 20 2003 |
Fingerprint
ASJC Scopus subject areas
- Genetics
Cite this
Arteriogenesis induced by intramyocardial vascular endothelial growth factor 165 gene transfer in chronically ischemic pigs. / Crottogini, Alberto; Martínez, Verónica; De Lorenzi, Andrea; Telayna, Juan; Mele, Aníbal; Fernández, José L.; Marangunich, Laura; Criscuolo, Marcelo; Capogrossi, Maurizio C.; Laguens, Rubén; Meckert, Patricia Cabeza; Vera Janavel, Gustavo; Lascano, Elena; Negroni, Jorge; Del Valle, Héctor; Dulbecco, Eduardo; Werba, Pablo; Cuniberti, Luis.
In: Human Gene Therapy, Vol. 14, No. 14, 20.09.2003, p. 1307-1318.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Arteriogenesis induced by intramyocardial vascular endothelial growth factor 165 gene transfer in chronically ischemic pigs
AU - Crottogini, Alberto
AU - Martínez, Verónica
AU - De Lorenzi, Andrea
AU - Telayna, Juan
AU - Mele, Aníbal
AU - Fernández, José L.
AU - Marangunich, Laura
AU - Criscuolo, Marcelo
AU - Capogrossi, Maurizio C.
AU - Laguens, Rubén
AU - Meckert, Patricia Cabeza
AU - Vera Janavel, Gustavo
AU - Lascano, Elena
AU - Negroni, Jorge
AU - Del Valle, Héctor
AU - Dulbecco, Eduardo
AU - Werba, Pablo
AU - Cuniberti, Luis
PY - 2003/9/20
Y1 - 2003/9/20
N2 - Exogenous vascular endothelial growth factor (VEGF) improves tissue perfusion in large animals and humans with chronic myocardial ischemia. Because tissue perfusion is mainly dependent on the arteriolar tree, we hypothesized that the neovascularizing effect of VEGF should include arteriogenesis, an effect not as yet described in large mammalian models of myocardial ischemia. In the present study we investigated the effect of intramyocardial plasmid-mediated human VEGF165 gene transfer (pVEGF165) on the proliferation of vessels with smooth muscle in a pig model of myocardial ischemia. In addition, we assessed the effect of treatment on capillary growth, myocardial perfusion, myocardial function and collateralization. Three weeks after positioning of an Ameroid constrictor (Research Instruments SW, Escondido, CA) in the left circumflex artery, pigs underwent basal perfusion (single-photon emission computed tomography [SPECT] with 99mTc-sestamibi) and regional function (echocardiography) studies at rest and under dobutamine stress, and were then randomly assigned to receive transepicardial injection of pVEGF165 3.8 mg (n = 8) or placebo (empty plasmid, n = 8). All experimental steps and data analysis were clone in a blinded fashion. Five weeks later, pVEGF165-treated pigs showed a significantly higher density of small (8-50 μm in diameter) vessels with smooth muscle, higher density of capillaries, and improved myocardial perfusion. These results indicate an arteriogenic effect of VEGF in a large mammalian model of myocardial ischemia and encourage the use of VEGF to promote arteriolar growth in patients with severe coronary artery disease.
AB - Exogenous vascular endothelial growth factor (VEGF) improves tissue perfusion in large animals and humans with chronic myocardial ischemia. Because tissue perfusion is mainly dependent on the arteriolar tree, we hypothesized that the neovascularizing effect of VEGF should include arteriogenesis, an effect not as yet described in large mammalian models of myocardial ischemia. In the present study we investigated the effect of intramyocardial plasmid-mediated human VEGF165 gene transfer (pVEGF165) on the proliferation of vessels with smooth muscle in a pig model of myocardial ischemia. In addition, we assessed the effect of treatment on capillary growth, myocardial perfusion, myocardial function and collateralization. Three weeks after positioning of an Ameroid constrictor (Research Instruments SW, Escondido, CA) in the left circumflex artery, pigs underwent basal perfusion (single-photon emission computed tomography [SPECT] with 99mTc-sestamibi) and regional function (echocardiography) studies at rest and under dobutamine stress, and were then randomly assigned to receive transepicardial injection of pVEGF165 3.8 mg (n = 8) or placebo (empty plasmid, n = 8). All experimental steps and data analysis were clone in a blinded fashion. Five weeks later, pVEGF165-treated pigs showed a significantly higher density of small (8-50 μm in diameter) vessels with smooth muscle, higher density of capillaries, and improved myocardial perfusion. These results indicate an arteriogenic effect of VEGF in a large mammalian model of myocardial ischemia and encourage the use of VEGF to promote arteriolar growth in patients with severe coronary artery disease.
UR - http://www.scopus.com/inward/record.url?scp=10744230276&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=10744230276&partnerID=8YFLogxK
U2 - 10.1089/104303403322319390
DO - 10.1089/104303403322319390
M3 - Article
VL - 14
SP - 1307
EP - 1318
JO - Human Gene Therapy
JF - Human Gene Therapy
SN - 1043-0342
IS - 14
ER -