|
|
| PMID |
|
|
| TITLE |
|
| Regulation of vascular leak and recovery from ischemic injury by general and VE-cadherin-restricted miRNA antagonists of miR-27. |
|
| ABSTRACT |
|
|
|
| Cellular junctions are essential to the normal functioning of the endothelium and control angiogenesis, tissue leak, and inflammation. From a screen of micro RNAs (miRNAs) altered in in vitro angiogenesis, we selected a subset predicted to target junctional molecules. MiR-27a was rapidly downregulated upon stimulation of in vitro angiogenesis, and its level of expression is reduced in neovessels in vivo. The downregulation of miR-27a was essential for angiogenesis because ectopic expression of miR-27a blocked capillary tube formation and angiogenesis. MiR-27a targets the junctional, endothelial-specific cadherin, VE-cadherin. Consistent with this, vascular permeability to vascular endothelial growth factor in mice is reduced by administration of a general miR-27 inhibitor. To determine that VE-cadherin was the dominant target of miR-27a function, we used a novel technology with "Blockmirs," inhibitors that bind to the miR-27 binding site in VE-cadherin. The Blockmir CD5-2 demonstrated specificity for VE-cadherin and inhibited vascular leak in vitro and in vivo. Furthermore, CD5-2 reduced edema, increased capillary density, and potently enhanced recovery from ischemic limb injury in mice. The Blockmir technology offers a refinement in the use of miRNAs, especially for therapy. Further, targeting of endothelial junctional molecules by miRNAs has clinical potential, especially in diseases associated with vascular leak. |
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| DATE PUBLISHED |
|
|
| HISTORY |
|
| PUBSTATUS |
PUBSTATUSDATE |
| entrez |
2013/09/07 06:00 |
| pubmed |
2013/09/07 06:00 |
| medline |
2013/12/18 06:00 |
|
| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Young JA |
|
Young |
Jennifer A |
JA |
|
Centre for the Endothelium, Vascular Biology Program, Centenary Institute, and University of Sydney, Sydney, Australia; |
| Ting KK |
|
Ting |
Ka Ka |
KK |
|
|
| Li J |
|
Li |
Jia |
J |
|
|
| Moller T |
|
Moller |
Thorleif |
T |
|
|
| Dunn L |
|
Dunn |
Louise |
L |
|
|
| Lu Y |
|
Lu |
Ying |
Y |
|
|
| Moses J |
|
Moses |
Joshua |
J |
|
|
| Prado-Lourenço L |
|
Prado-Lourenço |
Leonel |
L |
|
|
| Khachigian LM |
|
Khachigian |
Levon M |
LM |
|
|
| Ng M |
|
Ng |
Martin |
M |
|
|
| Gregory PA |
|
Gregory |
Philip A |
PA |
|
|
| Goodall GJ |
|
Goodall |
Gregory J |
GJ |
|
|
| Tsykin A |
|
Tsykin |
Anna |
A |
|
|
| Lichtenstein I |
|
Lichtenstein |
Ilana |
I |
|
|
| Hahn CN |
|
Hahn |
Christopher N |
CN |
|
|
| Tran N |
|
Tran |
Nham |
N |
|
|
| Shackel N |
|
Shackel |
Nicholas |
N |
|
|
| Kench JG |
|
Kench |
James G |
JG |
|
|
| McCaughan G |
|
McCaughan |
Geoffrey |
G |
|
|
| Vadas MA |
|
Vadas |
Mathew A |
MA |
|
|
| Gamble JR |
|
Gamble |
Jennifer R |
JR |
|
|
|
| INVESTIGATORS |
|
|
| JOURNAL |
|
| VOLUME: 122 |
| ISSUE: 16 |
| TITLE: Blood |
| ISOABBREVIATION: Blood |
| YEAR: 2013 |
| MONTH: Oct |
| DAY: 17 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1528-0020 |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
|
| MEDLINETA: Blood |
| COUNTRY: United States |
| ISSNLINKING: 0006-4971 |
| NLMUNIQUEID: 7603509 |
|
| PUBLICATION TYPE |
|
| PUBLICATIONTYPE TEXT |
| Journal Article |
| Research Support, Non-U.S. Gov't |
|
| COMMENTS AND CORRECTIONS |
|
| REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
| ErratumIn |
Blood. 2014 Nov 6;124(19):3034 |
|
|
|
| GRANTS |
|
|
| GENERAL NOTE |
|
|
| KEYWORDS |
|
|
| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Animals |
|
| Antigens, CD |
metabolism |
| Binding Sites |
metabolism |
| Cadherins |
metabolism |
| Capillary Permeability |
metabolism |
| Edema |
pathology |
| Gene Expression Regulation |
pathology |
| HEK293 Cells |
pathology |
| Human Umbilical Vein Endothelial Cells |
pathology |
| Humans |
pathology |
| Ischemia |
pathology |
| Liver Cirrhosis |
pathology |
| Mice |
pathology |
| Mice, Inbred C57BL |
pathology |
| MicroRNAs |
metabolism |
| Neovascularization, Pathologic |
metabolism |
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
|
| CHEMICALS |
|
| REGISTRYNUMBER |
NAMEOFSUBSTANCE |
| 0 |
Antigens, CD |
| 0 |
Cadherins |
| 0 |
MIRN27 microRNA, human |
| 0 |
MicroRNAs |
| 0 |
cadherin 5 |
|
| OTHER ID's |
|
|
|
