2007 Fiscal Year Final Research Report Summary
Cardiovascular regeneration therapy by placental growth factor gene transfer in coronary artery disease.
| Project/Area Number |
18590797
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Foundation for Biomedical Research and Innovation |
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Principal Investigator |
KAWAMOTO Atsuhiko Foundation for Biomedical Research and Innovation, Institute of Biomedical Research and Innovation, Vascular Regeneration Research Group, Senior Researcher (00275330)
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| Co-Investigator(Kenkyū-buntansha) |
MURASAWA Satoshi Institute of Biomedical Research and Innovation, Vascular Regeneration Research Group, Researcher (20359441)
ASAHARA Takayuki Tokai University, School of Medicine, Department of Regenerative Medicine Science, Professor (20246200)
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| Project Period (FY) |
2006 – 2007
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| Keywords | cardiovascular medicine / regeneration / vasculogenesis |
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| Research Abstract |
In 2007, we investigated therapeutic potential of intramyocardial transfer of human placental growth factor(hPlGF) plasmid in rats with acute myocardial infarction. Histological capillary density at day 28 was significantly greater in rats receiving hPlGF compared with those receiving empty vector(Mock) . Left ventricular(LV) fibrosis and myocardial apoptosis was significantly inhibited in hPlGF group than Mock group. Echocardiographic LV functional parameters such as fractional shortening and regional wall motion score were significantry preserved in hPlGF group than Mock group.
In 2008, we performed catheter-based, intramyocardial injection of hPlGF plasmid(500μg or 1000μg) into swine with chronic myocardial ischemia. Chronic myocardial ischemia was induced by ameroid constrictor placement around left circumflex artery. Four weels after the induction, LV ischemic area was identified by NOGA electromechanical mapping. The hPlGF or empty vector plasmid was intramyocardially injected into the ischemic area with Myostar injection catheter. Improvement of LV ischemic area by NOGA mapping, LV functional parameters by echocardiography and angiographic collateral score was significantly greater in hPlGF groups than Mock group. Histological capillary density was also greater in hPlGF groups than Mock group. These parameters were similar in 500μg and 1000μg of PlGF groups.
PlGF gene therapy was effective for attenuation of myocardial ischemia and improvement of LV function in both small and large animal models of myocardial ischemia. These findings suggest the promising outcome in the future clinical application of this novel angiogenic therapy.
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