Microenvironmental VEGF distribution is critical for stable and functional vessel growth in ischemia.

Microenvironmental VEGF distribution is critical for stable and functional vessel growth in ischemia. Research Abstract Details 

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Microenvironmental VEGF distribution is critical for stable and functional vessel growth in ischemia. Abstract Text:

Georges von Degenfeld,Andrea Banfi,Matthew L Springer,Roger A Wagner,Johannes Jacobi,Clare R Ozawa,Milton J Merchant,John P Cooke,Helen M Blau,

The critical role of vascular endothelial growth factor (VEGF) expression levels in developmental angiogenesis is well established. Nonetheless, the effects of different local (microenvironmental) VEGF concentrations in ischemia have not been studied in the adult organism, and VEGF delivery to patients has been disappointing. Here, we demonstrate the existence of both lower and upper threshold levels of microenvironmental VEGF concentrations for the induction of therapeutic vessel growth in ischemia. In the ischemic hind limb, implantation of myoblasts transduced to express VEGF164 at different levels per cell increased blood flow only moderately, and vascular leakage and aberrant preangiomatous vessels were always induced. When the same total dose was uniformly distributed by implanting a monoclonal population derived from a single VEGF-expressing myoblast, blood flow was fully restored to nonischemic levels, collateral growth was induced, and ischemic damage was prevented. Hemangiomas were avoided and only normal, pericyte-covered vessels were induced persisting over 15 mo. Surprisingly, clones uniformly expressing either lower or higher VEGF levels failed to provide any functional benefit. A biphasic effect of VEGF dose on vessel number and diameter was found. Blood flow was only improved if vessels were increased both in size and in number. Microenvironmental VEGF concentrations determine efficacy and safety in a therapeutic setting.

Microenvironmental VEGF distribution is critical for stable and functional vessel growth in ischemia. Publishing Authors By Initials

G von Degenfeld,A Banfi,ML Springer,RA Wagner,J Jacobi,CR Ozawa,MJ Merchant,JP Cooke,HM Blau,

For similar peptides: intercellular signaling peptides and proteins: angiogenic proteins: vascular endothelial growth factors: vascular endothelial growth factor a research abstracts see: peptides: intercellular signaling peptides and proteins: angiogenic proteins: vascular endothelial growth factors: vascular endothelial growth factor a research

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Microenvironmental VEGF distribution is critical for stable and functional vessel growth in ischemia. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The FASEB journal : official publication of the Fe

VOLUME: 20

Page Numbers: 2657-9

Journal Abbreviation: FASEB J.

ISSN: 1530-6860

DAY: 9

MONTH: 11

YEAR: 2006

Microenvironmental VEGF distribution is critical for stable and functional vessel growth in ischemia. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8804484

Microenvironmental VEGF distribution is critical for stable and functional vessel growth in ischemia. Keywords Mesh Terms:

KEYWORDS: Vascular Endothelial Growth Factor A

MESH TERMS: metabolism

Chemical & Substance for Abstract: Microenvironmental VEGF distribution is critical for stable and functional vessel growth in ischemia. Information

Substance Name: vascular endothelial growth factor A, mo

Registry Number: 0

Grant and Affiliation Information for Microenvironmental VEGF distribution is critical for stable and functional vessel growth in ischemia.

AFFILIATION: Baxter Laboratory in Genetic Pharmacology, Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, CA 94305-5175, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL065572

ACRONYM: HL

MEDLINETA: FASEB J

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