RGD Reference Report - Estradiol regulates angiopoietin-1 mRNA expression through estrogen receptor-alpha in a rodent experimental stroke model. - Rat Genome Database

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Estradiol regulates angiopoietin-1 mRNA expression through estrogen receptor-alpha in a rodent experimental stroke model.

Authors: Ardelt, AA  McCullough, LD  Korach, KS  Wang, MM  Munzenmaier, DH  Hurn, PD 
Citation: Ardelt AA, etal., Stroke. 2005 Feb;36(2):337-41. Epub 2005 Jan 6.
RGD ID: 1626166
Pubmed: PMID:15637314   (View Abstract at PubMed)
DOI: DOI:10.1161/01.STR.0000153795.38388.72   (Journal Full-text)

BACKGROUND AND PURPOSE: Female, compared with male, animals are protected from cerebral ischemic injury. Physiological concentrations of 17beta-estradiol (E2) reduce damage in experimental stroke. E2 augments angiogenesis in reproductive organs and noncerebral vascular beds. We hypothesized that E2 protects brain in stroke through modulation of angiogenesis. We quantified molecular markers of angiogenesis and capillary density before and after unilateral middle cerebral artery occlusion (MCAO). METHODS: Female animals were ovariectomized, treated with 25 microg E2 or placebo implants, and subjected to 2-hour MCAO and 22 hours of reperfusion. Brain angiopoietin-1 (Ang-1), Ang-2, Tie-1, Tie-2, vascular endothelial growth factor (VEGF), VEGF R1, and VEGF R2 mRNA levels were determined by RNAse protection assays, and CD31-positive vessels were counted. RESULTS: E2, but not ischemia, upregulated cerebral Ang-1 mRNA by 49%. Capillary density was higher in the brains of E2-treated animals. In estrogen receptor-alpha knockout (ERKO) mice, E2-mediated induction of Ang-1 mRNA was absent relative to wild-type littermates. CONCLUSIONS: These results suggest that E2 increases Ang-1 and enhances capillary density in brain under basal conditions, priming the MCA territory for survival after experimental focal ischemia.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Stroke  ISOAngpt2 (Rattus norvegicus)1626166; 1626166mRNA:increased expression:brain (rat)RGD 
Stroke  IEP 1626166mRNA:increased expression:brain (rat)RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to estrogen  IEP 1626166 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Angpt1  (angiopoietin 1)
Angpt2  (angiopoietin 2)

Genes (Mus musculus)
Angpt2  (angiopoietin 2)

Genes (Homo sapiens)
ANGPT2  (angiopoietin 2)


Additional Information