RGD Reference Report - Angiotensin-(1-7) inhibits growth of cardiac myocytes through activation of the mas receptor. - Rat Genome Database

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Angiotensin-(1-7) inhibits growth of cardiac myocytes through activation of the mas receptor.

Authors: Tallant, EA  Ferrario, CM  Gallagher, PE 
Citation: Tallant EA, etal., Am J Physiol Heart Circ Physiol. 2005 Oct;289(4):H1560-6. Epub 2005 Jun 10.
RGD ID: 1581938
Pubmed: PMID:15951342   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpheart.00941.2004   (Journal Full-text)

Peptide hormones such as ANG II and endothelin contribute to cardiac remodeling after myocardial infarction by stimulating myocyte hypertrophy and myofibroblast proliferation. In contrast, angiotensin-(1-7) [ANG-(1-7)] infusion after myocardial infarction reduced myocyte size and attenuated ventricular dysfunction and remodeling. We measured the effect of ANG-(1-7) on protein and DNA synthesis in cultured neonatal rat myocytes to assess the role of the heptapeptide in cell growth. ANG-(1-7) significantly attenuated either fetal bovine serum- or endothelin-1-stimulated [(3)H]leucine incorporation into myocytes with no effect on [(3)H]thymidine incorporation. [d-Ala(7)]-ANG-(1-7), the selective ANG type 1-7 (AT(1-7)) receptor antagonist, blocked the ANG-(1-7)-mediated reduction in protein synthesis in cardiac myocytes, whereas the AT(1) and AT(2) angiotensin peptide receptors were ineffective. Serum-stimulated ERK1/ERK2 mitogen-activated protein kinase activity was significantly decreased by ANG-(1-7) in myocytes, a response that was also blocked by [d-Ala(7)]-ANG-(1-7). Both rat heart and cardiac myocytes express the mRNA for the mas receptor, and a 59-kDa immunoreactive protein was identified in both extracts of rat heart and cultured myocytes by Western blot hybridization with the use of an antibody to mas, an ANG-(1-7) receptor. Transfection of cultured myocytes with an antisense oligonucleotide to the mas receptor blocked the ANG-(1-7)-mediated inhibition of serum-stimulated MAPK activation, whereas a sense oligonucleotide was ineffective. These results suggest that ANG-(1-7) reduces the growth of cardiomyocytes through activation of the mas receptor. Because ANG-(1-7) is elevated after treatment with angiotensin-converting enzyme inhibitors or AT(1) receptor blockers, ANG-(1-7) may contribute to their beneficial effects on cardiac dysfunction and ventricular remodeling after myocardial infarction.



Gene Ontology Annotations    

Biological Process

Cellular Component
cell surface  (IDA)

Molecular Pathway Annotations    
Objects Annotated

Genes (Rattus norvegicus)
Agt  (angiotensinogen)
Mas1  (MAS1 proto-oncogene, G protein-coupled receptor)

Genes (Mus musculus)
Agt  (angiotensinogen)

Genes (Homo sapiens)
AGT  (angiotensinogen)


Additional Information