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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2006-7-10
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pubmed:abstractText |
Vascular endothelial growth factor (VEGF) exerts crucial functions during pathological angiogenesis and normal physiology. We observed increased hematocrit (60-75%) after high-grade inhibition of VEGF by diverse methods, including adenoviral expression of soluble VEGF receptor (VEGFR) ectodomains, recombinant VEGF Trap protein and the VEGFR2-selective antibody DC101. Increased production of red blood cells (erythrocytosis) occurred in both mouse and primate models, and was associated with near-complete neutralization of VEGF corneal micropocket angiogenesis. High-grade inhibition of VEGF induced hepatic synthesis of erythropoietin (Epo, encoded by Epo) >40-fold through a HIF-1alpha-independent mechanism, in parallel with suppression of renal Epo mRNA. Studies using hepatocyte-specific deletion of the Vegfa gene and hepatocyte-endothelial cell cocultures indicated that blockade of VEGF induced hepatic Epo by interfering with homeostatic VEGFR2-dependent paracrine signaling involving interactions between hepatocytes and endothelial cells. These data indicate that VEGF is a previously unsuspected negative regulator of hepatic Epo synthesis and erythropoiesis and suggest that levels of Epo and erythrocytosis could represent noninvasive surrogate markers for stringent blockade of VEGF in vivo.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1078-8956
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pubmed:author |
pubmed-author:ChartierCecileC,
pubmed-author:GarciaJoseph AJA,
pubmed-author:HefnerColleenC,
pubmed-author:HoffmanJanaJ,
pubmed-author:HolashJoceylnJ,
pubmed-author:JiangShellyS,
pubmed-author:JohnsonRandall SRS,
pubmed-author:KuoCalvin JCJ,
pubmed-author:KuypersFrans AFA,
pubmed-author:LeeJeng-ShinJS,
pubmed-author:MaLisaL,
pubmed-author:MaherJacquelyn JJJ,
pubmed-author:MulliganRichard CRC,
pubmed-author:NayakNihar RNR,
pubmed-author:NiyakNihar RNR,
pubmed-author:ParkSang-kiSK,
pubmed-author:RudgeJohn SJS,
pubmed-author:SchrierStanley LSL,
pubmed-author:SundramUmaU,
pubmed-author:TamBetty Y YBY,
pubmed-author:WeiKevinK,
pubmed-author:WuGraceG,
pubmed-author:YancopoulosGeorge DGD,
pubmed-author:YuanJennyJ
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pubmed:issnType |
Print
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pubmed:volume |
12
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
793-800
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16799557-Animals,
pubmed-meshheading:16799557-Erythropoietin,
pubmed-meshheading:16799557-Hematocrit,
pubmed-meshheading:16799557-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:16799557-Liver,
pubmed-meshheading:16799557-Mice,
pubmed-meshheading:16799557-Mice, Inbred C57BL,
pubmed-meshheading:16799557-Mice, SCID,
pubmed-meshheading:16799557-Mice, Transgenic,
pubmed-meshheading:16799557-Models, Animal,
pubmed-meshheading:16799557-Polycythemia,
pubmed-meshheading:16799557-Receptors, Vascular Endothelial Growth Factor,
pubmed-meshheading:16799557-Retinal Vessels,
pubmed-meshheading:16799557-Vascular Endothelial Growth Factor A
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pubmed:year |
2006
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pubmed:articleTitle |
VEGF modulates erythropoiesis through regulation of adult hepatic erythropoietin synthesis.
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pubmed:affiliation |
Division of Hematology, Stanford University School of Medicine, 269 Campus Drive, CCSR 1155, Stanford, California, 94305, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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