TY - JOUR
T1 - Adenovirus-mediated acidic fibroblast growth factor gene transfer induces angiogenesis in the nonischemic rabbit heart
AU - Safi, Jorge
AU - DiPaula, Anthony F.
AU - Riccioni, Teresa
AU - Kajstura, Jan
AU - Ambrosio, Giuseppe
AU - Becker, Lewis C.
AU - Anversa, Piero
AU - Capogrossi, Maurizio C.
PY - 1999/11
Y1 - 1999/11
N2 - Most patients with severe coronary artery disease have normal baseline myocardial blood flow. Therefore, interventions aimed at inducing therapeutic angiogenesis in these patients should cause new blood vessel growth in the heart in the absence of chronic ischemia. It was examined whether adenovirus- mediated gene transfer of recombinant, secreted acidic fibroblast growth factor (sp+aFGF1-154), next to a major epicardial artery, may induce neovascularization and reduce the risk region for myocardial infarction upon coronary ligation near the injection site. Fifteen days prior to coronary artery occlusion, rabbits were treated with intramyocardial injections of AdCMV.sp+aFGF1-154, the control vector AdCMV.NLSβgal (1 x 109 plaque- forming units), or saline. Messenger RNA transcripts for aFGF1-154 were present up to 12 days after injection in the tissues exposed to AdCMV.aFGF1-154. Following coronary artery occlusion rabbits treated with AdCMV.sp+aFGF1-154 showed a 50% reduction of the risk region for myocardial infarction (P <0.01 vs control). Histologic analysis showed a twofold increase in length density of intramural coronary arterioles (P <0.01 vs control) and a 17% increase in length density of the capillary network (P <0.001) in the myocardium exposed to AdCMV.sp+aFGF1-154. Thus, gene therapy with AdCMV.sp+aFGF1-154 can induce angiogenesis in the absence of chronic ischemia. The newly formed collateral blood vessels provide an anatomical basis for the reduction in the risk region for myocardial infarction upon subsequent occlusion of the coronary artery in proximity of the site where angiogenesis was induced.
AB - Most patients with severe coronary artery disease have normal baseline myocardial blood flow. Therefore, interventions aimed at inducing therapeutic angiogenesis in these patients should cause new blood vessel growth in the heart in the absence of chronic ischemia. It was examined whether adenovirus- mediated gene transfer of recombinant, secreted acidic fibroblast growth factor (sp+aFGF1-154), next to a major epicardial artery, may induce neovascularization and reduce the risk region for myocardial infarction upon coronary ligation near the injection site. Fifteen days prior to coronary artery occlusion, rabbits were treated with intramyocardial injections of AdCMV.sp+aFGF1-154, the control vector AdCMV.NLSβgal (1 x 109 plaque- forming units), or saline. Messenger RNA transcripts for aFGF1-154 were present up to 12 days after injection in the tissues exposed to AdCMV.aFGF1-154. Following coronary artery occlusion rabbits treated with AdCMV.sp+aFGF1-154 showed a 50% reduction of the risk region for myocardial infarction (P <0.01 vs control). Histologic analysis showed a twofold increase in length density of intramural coronary arterioles (P <0.01 vs control) and a 17% increase in length density of the capillary network (P <0.001) in the myocardium exposed to AdCMV.sp+aFGF1-154. Thus, gene therapy with AdCMV.sp+aFGF1-154 can induce angiogenesis in the absence of chronic ischemia. The newly formed collateral blood vessels provide an anatomical basis for the reduction in the risk region for myocardial infarction upon subsequent occlusion of the coronary artery in proximity of the site where angiogenesis was induced.
KW - Adenovirus
KW - aFGF
KW - Angiogenesis
KW - Collateral circulation
KW - Gene therapy
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U2 - 10.1006/mvre.1999.2165
DO - 10.1006/mvre.1999.2165
M3 - Article
C2 - 10527767
AN - SCOPUS:0032713818
VL - 58
SP - 238
EP - 249
JO - Microvascular Research
JF - Microvascular Research
SN - 0026-2862
IS - 3
ER -