Unknown

Dataset Information

0

Cardiac pressure overload hypertrophy is differentially regulated by ?-adrenergic receptor subtypes.


ABSTRACT: In isolated myocytes, hypertrophy induced by norepinephrine is mediated via ?(1)-adrenergic receptors (ARs) and not ?-ARs. However, mice with deletions of both major cardiac ?(1)-ARs still develop hypertrophy in response to pressure overload. Our purpose was to better define the role of ?-AR subtypes in regulating cardiac hypertrophy in vivo, important given the widespread clinical use of ?-AR antagonists and the likelihood that patients treated with these agents could develop conditions of further afterload stress. Mice with deletions of ?(1), ?(2), or both ?(1)- and ?(2)-ARs were subjected to transverse aortic constriction (TAC). After 3 wk, ?(1)(-/-) showed a 21% increase in heart to body weight vs. sham controls, similar to wild type, whereas ?(2)(-/-) developed exaggerated (49% increase) hypertrophy. Only when both ?-ARs were ablated (?(1)?(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 ?(1)?(2)(-/-) compared with the other genotypes, whereas transforming growth factor-?(2), a positive mediator of hypertrophy was upregulated in all genotypes except the ?(1)?(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, Hif1?, and p53) play a role in compensated cardiac hypertrophy. Pressure overload hypertrophy in vivo is dependent on a coordination of signaling through both ?(1)- and ?(2)-ARs, mediated through several key cardiac remodeling pathways. Angiogenesis is not a prerequisite for compensated cardiac hypertrophy.

SUBMITTER: Zhao M 

PROVIDER: S-EPMC3197363 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications

Cardiac pressure overload hypertrophy is differentially regulated by β-adrenergic receptor subtypes.

Zhao Mingming M   Fajardo Giovanni G   Urashima Takashi T   Spin Joshua M JM   Poorfarahani Sara S   Rajagopalan Viswanathan V   Huynh Diem D   Connolly Andrew A   Quertermous Thomas T   Bernstein Daniel D  

American journal of physiology. Heart and circulatory physiology 20110624 4


In isolated myocytes, hypertrophy induced by norepinephrine is mediated via α(1)-adrenergic receptors (ARs) and not β-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 β-AR subtypes in regulating cardiac hypertrophy in vivo, important given the widespread clinical use of β-AR antagonists and the likelihood that patients treated with these agents could develop conditions of furt  ...[more]

Similar Datasets

| S-EPMC8741968 | biostudies-literature
2005-06-29 | GSE2459 | GEO
2002-07-30 | GSE76 | GEO
| S-EPMC10022866 | biostudies-literature
| S-EPMC2610480 | biostudies-literature
| S-EPMC7363709 | biostudies-literature
| S-EPMC5082686 | biostudies-literature
| S-EPMC2259198 | biostudies-literature
2006-07-04 | GSE5129 | GEO
| S-EPMC3929275 | biostudies-literature