In:
American Journal of Physiology-Heart and Circulatory Physiology, American Physiological Society, Vol. 301, No. 4 ( 2011-10), p. H1461-H1470
Abstract:
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 further afterload stress. Mice with deletions of β 1 , β 2 , or both β 1 - and β 2 -ARs were subjected to transverse aortic constriction (TAC). After 3 wk, β 1 −/− showed a 21% increase in heart to body weight vs. sham controls, similar to wild type, whereas β 2 −/− developed exaggerated (49% increase) hypertrophy. Only when both β-ARs were ablated (β 1 β 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 β 1 β 2 −/− compared with the other genotypes, whereas transforming growth factor-β 2 , a positive mediator of hypertrophy was upregulated in all genotypes except the β 1 β 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 β 1 - and β 2 -ARs, mediated through several key cardiac remodeling pathways. Angiogenesis is not a prerequisite for compensated cardiac hypertrophy.
Type of Medium:
Online Resource
ISSN:
0363-6135
,
1522-1539
DOI:
10.1152/ajpheart.00453.2010
Language:
English
Publisher:
American Physiological Society
Publication Date:
2011
detail.hit.zdb_id:
1477308-9
SSG:
12
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