RGD Reference Report - Overexpression of angiotensin II type I receptor in cardiomyocytes induces cardiac hypertrophy and remodeling. - Rat Genome Database

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Overexpression of angiotensin II type I receptor in cardiomyocytes induces cardiac hypertrophy and remodeling.

Authors: Paradis, P  Dali-Youcef, N  Paradis, FW  Thibault, G  Nemer, M 
Citation: Paradis P, etal., Proc Natl Acad Sci U S A 2000 Jan 18;97(2):931-6.
RGD ID: 737777
Pubmed: PMID:10639182   (View Abstract at PubMed)
PMCID: PMC15433   (View Article at PubMed Central)

Angiotensin II (AII) is a major determinant of arterial pressure and volume homeostasis, mainly because of its vascular action via the AII type 1 receptor (AT1R). AII has also been implicated in the development of cardiac hypertrophy because angiotensin I-converting enzyme inhibitors and AT1R antagonists prevent or regress ventricular hypertrophy in animal models and in human. However, because these treatments impede the action of AII at cardiac as well as vascular levels, and reduce blood pressure, it has been difficult to determine whether AII action on the heart is direct or a consequence of pressure-overload. To determine whether AII can induce cardiac hypertrophy directly via myocardial AT1R in the absence of vascular changes, transgenic mice overexpressing the human AT1R under the control of the mouse alpha-myosin heavy chain promoter were generated. Cardiomyocyte-specific overexpression of AT1R induced, in basal conditions, morphologic changes of myocytes and nonmyocytes that mimic those observed during the development of cardiac hypertrophy in human and in other mammals. These mice displayed significant cardiac hypertrophy and remodeling with increased expression of ventricular atrial natriuretic factor and interstitial collagen deposition and died prematurely of heart failure. Neither the systolic blood pressure nor the heart rate were changed. The data demonstrate a direct myocardial role for AII in the development of cardiac hypertrophy and failure and provide a useful model to elucidate the mechanisms of action of AII in the pathogenesis of cardiac diseases.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Cardiomegaly  IMP 737777 RGD 
Cardiomegaly  ISOAGTR1 (Homo sapiens)737777; 737777 RGD 
Cardiomegaly  IAGP 737777 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Agtr1a  (angiotensin II receptor, type 1a)

Genes (Mus musculus)
Agtr1a  (angiotensin II receptor, type 1a)
Agtr1b  (angiotensin II receptor, type 1b)

Genes (Homo sapiens)
AGTR1  (angiotensin II receptor type 1)


Additional Information