Cardiac pressure overload hypertrophy is differentially regulated by ß-adrenergic receptor subtypes.
Am J Physiol Heart Circ Physiol
; 301(4): H1461-70, 2011 Oct.
Article
em En
| MEDLINE
| ID: mdl-21705675
ABSTRACT
In isolated myocytes, hypertrophy induced by norepinephrine is mediated via α(1)-adrenergic receptors (ARs) and not ß-ARs. However, mice with deletions of both major cardiac α(1)-ARs still develop hypertrophy in response to pressure overload. Our purpose was to better define the role of ß-AR subtypes in regulating cardiac hypertrophy in vivo, important given the widespread clinical use of ß-AR antagonists and the likelihood that patients treated with these agents could develop conditions of further afterload stress. Mice with deletions of ß(1), ß(2), or both ß(1)- and ß(2)-ARs were subjected to transverse aortic constriction (TAC). After 3 wk, ß(1)(-/-) showed a 21% increase in heart to body weight vs. sham controls, similar to wild type, whereas ß(2)(-/-) developed exaggerated (49% increase) hypertrophy. Only when both ß-ARs were ablated (ß(1)ß(2)(-/-)) was hypertrophy totally abolished. Cardiac function was preserved in all genotypes. Several known inhibitors of cardiac hypertrophy (FK506 binding protein 5, thioredoxin interacting protein, and S100A9) were upregulated in ß(1)ß(2)(-/-) compared with the other genotypes, whereas transforming growth factor-ß(2), a positive mediator of hypertrophy was upregulated in all genotypes except the ß(1)ß(2)(-/-). In contrast to recent reports suggesting that angiogenesis plays a critical role in regulating cardiac hypertrophy-induced heart failure, we found no evidence that angiogenesis or its regulators (VEGF, Hif1α, and p53) play a role in compensated cardiac hypertrophy. Pressure overload hypertrophy in vivo is dependent on a coordination of signaling through both ß(1)- and ß(2)-ARs, mediated through several key cardiac remodeling pathways. Angiogenesis is not a prerequisite for compensated cardiac hypertrophy.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Receptores Adrenérgicos beta
/
Cardiomegalia
/
Coração
/
Hipertensão
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Am J Physiol Heart Circ Physiol
Assunto da revista:
CARDIOLOGIA
/
FISIOLOGIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos