RGD Reference Report - Neuregulin in cardiac hypertrophy in rats with aortic stenosis. Differential expression of erbB2 and erbB4 receptors. - Rat Genome Database

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Neuregulin in cardiac hypertrophy in rats with aortic stenosis. Differential expression of erbB2 and erbB4 receptors.

Authors: Rohrbach, S  Yan, X  Weinberg, EO  Hasan, F  Bartunek, J  Marchionni, MA  Lorell, BH 
Citation: Rohrbach S, etal., Circulation. 1999 Jul 27;100(4):407-12.
RGD ID: 1580989
Pubmed: PMID:10421602   (View Abstract at PubMed)

BACKGROUND: Neuregulins are a family of peptide growth factors that promote cell growth and viability. The potential role of neuregulin-erbB signaling in hypertrophic growth and later failure in the adult heart in vivo is not known. METHODS AND RESULTS: We used ribonuclease protection assays to quantify mRNA levels of neuregulin, erbB2, and erbB4 in left ventricular (LV) tissue and myocytes of normal rats and rats with aortic stenosis with pressure-overload hypertrophy 6 and 22 weeks after banding. At both stages of hypertrophy, Northern blot analyses of mRNA from LV myocytes showed upregulation of atrial natriuretic peptide, a molecular marker of hypertrophy (P<0.05). LV tissue neuregulin message levels were similar in animals with aortic stenosis compared with controls (P=NS) and were not detectable in myocytes. LV erbB2 and erbB4 message levels in LV tissue and myocytes were maintained during early compensatory hypertrophy in 6-week aortic stenosis animals compared with age-matched controls; in contrast, erbB2 and erbB4 message levels were depressed in 22-week aortic stenosis animals at the stage of early failure (both P<0.01 vs age-matched controls). Immunoblotting of erbB2 and erbB4 also showed normal protein levels in 6-week aortic stenosis animals compared with controls; however, erbB2 and erbB4 protein levels were depressed in 22-week aortic stenosis animals (48% decrease in erbB2, P<0.05, and 43% decrease in erbB4, P<0.01) relative to age-matched controls. CONCLUSIONS: The neuregulin receptors erbB2 and erbB4 are downregulated at both the message and protein levels at the stage of early failure in animals with chronic hypertrophy secondary to aortic stenosis. These data suggest a role for disabled erbB receptor signaling in the transition from compensatory hypertrophy to failure.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
congestive heart failure  ISOErbb2 (Rattus norvegicus)1580989; 1580989 RGD 
congestive heart failure  ISOErbb4 (Rattus norvegicus)1580989; 1580989associated with Aortic Valve Stenosis more ...RGD 
congestive heart failure  IEP 1580989 RGD 
congestive heart failure  IEP 1580989associated with Aortic Valve Stenosis more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Erbb2  (erb-b2 receptor tyrosine kinase 2)
Erbb4  (erb-b2 receptor tyrosine kinase 4)

Genes (Mus musculus)
Erbb2  (erb-b2 receptor tyrosine kinase 2)
Erbb4  (erb-b2 receptor tyrosine kinase 4)

Genes (Homo sapiens)
ERBB2  (erb-b2 receptor tyrosine kinase 2)
ERBB4  (erb-b2 receptor tyrosine kinase 4)


Additional Information