| Microarray profiling reveals CXCR4a is downregulated by blood flow in vivo and mediates collateral formation in zebrafish embryos. | |
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MedLine Citation:
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PMID: 19509081 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The response to hemodynamic force is implicated in a number of pathologies including collateral vessel development. However, the transcriptional effect of hemodynamic force is extremely challenging to examine in vivo in mammals without also detecting confounding processes such as hypoxia and ischemia. We therefore serially examined the transcriptional effect of preventing cardiac contraction in zebrafish embryos which can be deprived of circulation without experiencing hypoxia since they obtain sufficient oxygenation by diffusion. Morpholino antisense knock-down of cardiac troponin T2 (tnnt2) prevented cardiac contraction without affecting vascular development. Gene expression in whole embryo RNA from tnnt2 or control morphants at 36, 48, and 60 h postfertilization (hpf) was assessed using Affymetrix GeneChip Zebrafish Genome Arrays (>14,900 transcripts). We identified 308 differentially expressed genes between tnnt2 and control morphants. One such (CXCR4a) was significantly more highly expressed in tnnt2 morphants at 48 and 60 hpf than controls. In situ hybridization localized CXCR4a upregulation to endothelium of both tnnt2 morphants and gridlock mutants (which have an occluded aorta preventing distal blood flow). This upregulation appears to be of functional significance as either CXCR4a knock-down or pharmacologic inhibition impaired the ability of gridlock mutants to recover blood flow via collateral vessels. We conclude absence of hemodynamic force induces endothelial CXCR4a upregulation that promotes recovery of blood flow. |
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Authors:
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Ian M Packham; Caroline Gray; Paul R Heath; Paul G Hellewell; Philip W Ingham; David C Crossman; Marta Milo; Timothy J A Chico |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-06-09 |
Journal Detail:
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Title: Physiological genomics Volume: 38 ISSN: 1531-2267 ISO Abbreviation: Physiol. Genomics Publication Date: 2009 Aug |
Date Detail:
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Created Date: 2009-08-11 Completed Date: 2010-01-13 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9815683 Medline TA: Physiol Genomics Country: United States |
Other Details:
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Languages: eng Pagination: 319-27 Citation Subset: IM |
Affiliation:
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Medical Research Council Centre for Developmental and Biomedical Genetics, United Kingdom. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arterioles / growth & development Blood Flow Velocity Cluster Analysis Collateral Circulation Down-Regulation Embryo, Nonmammalian / embryology, metabolism* Female Gene Expression Profiling* Gene Expression Regulation, Developmental Gene Knockdown Techniques / methods In Situ Hybridization Male Myocardial Contraction Oligonucleotide Array Sequence Analysis / methods* Oligonucleotides, Antisense Receptors, CXCR4 / genetics* Reverse Transcriptase Polymerase Chain Reaction Troponin T / genetics Zebrafish / embryology, genetics* Zebrafish Proteins / genetics* |
| Grant Support | |
ID/Acronym/Agency:
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GR077544AIA//Wellcome Trust; //British Heart Foundation |
| Chemical | |
Reg. No./Substance:
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0/CXCR4a protein, zebrafish; 0/Oligonucleotides, Antisense; 0/Receptors, CXCR4; 0/Tnnt2 protein, zebrafish; 0/Troponin T; 0/Zebrafish Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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