RGD Reference Report - Egr-1 expression during neointimal development in flow-associated pulmonary hypertension. - Rat Genome Database

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Egr-1 expression during neointimal development in flow-associated pulmonary hypertension.

Authors: Dickinson, MG  Bartelds, B  Molema, G  Borgdorff, MA  Boersma, B  Takens, J  Weij, M  Wichers, P  Sietsma, H  Berger, RM 
Citation: Dickinson MG, etal., Am J Pathol. 2011 Nov;179(5):2199-209. doi: 10.1016/j.ajpath.2011.07.030. Epub 2011 Sep 13.
RGD ID: 10395308
Pubmed: PMID:21924231   (View Abstract at PubMed)
PMCID: PMC3204093   (View Article at PubMed Central)
DOI: DOI:10.1016/j.ajpath.2011.07.030   (Journal Full-text)

In flow-associated pulmonary arterial hypertension (PAH), increased pulmonary blood flow is an essential trigger for neointimal formation. Using microarray analysis, we recently found that the early growth response protein 1 (Egr-1) transcription factor is increased in experimental flow-associated end-stage PAH. Its role in PAH development is unknown. Here, we assessed the spatiotemporal expression of Egr-1 during neointimal development in flow-associated PAH. Flow-associated PAH was produced in rats by combining monocrotaline administration with an aortocaval shunt. Animals were sacrificed 1 day before or 1 day, 1 week, or 4 to 5 weeks after flow addition. Egr-1 expression was spatiotemporally assessed using laser microdissection, quantitative real-time PCR and immunohistochemistry. In addition, Egr-1 expression was assessed in a non-neointimal pulmonary hypertension model and in human PAH associated with congenital shunt. In 4 to 5 weeks, rats subjected to increased flow developed PAH with neointimal lesions. Egr-1 mRNA was increased 1 day after flow addition and in end-stage PAH, whereas monocrotaline only did not result in increased Egr-1 mRNA. Directly after flow addition, Egr-1 was expressed in endothelial cells. During disease development, Egr-1 protein expression increased and migrated throughout the vessel wall. In PAH patients, Egr-1 was expressed in vessels with media hypertrophy and neointimal lesions, including plexiform lesions. Thus, Egr-1 may be an important regulator in the development of pulmonary neointimal lesions induced by increased pulmonary blood flow.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
pulmonary hypertension  ISOEgr1 (Rattus norvegicus)10395308; 10395308 RGD 
pulmonary hypertension  IEP 10395308 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Egr1  (early growth response 1)

Genes (Mus musculus)
Egr1  (early growth response 1)

Genes (Homo sapiens)
EGR1  (early growth response 1)


Additional Information