Document Detail

Cardiac pressure overload hypertrophy is differentially regulated by β-adrenergic receptor subtypes.
MedLine Citation:
PMID:  21705675     Owner:  NLM     Status:  MEDLINE    
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.
Mingming Zhao; Giovanni Fajardo; Takashi Urashima; Joshua M Spin; Sara Poorfarahani; Viswanathan Rajagopalan; Diem Huynh; Andrew Connolly; Thomas Quertermous; Daniel Bernstein
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-06-24
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  301     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-09-29     Completed Date:  2011-11-22     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H1461-70     Citation Subset:  IM    
Department of Pediatrics, Stanford University, Stanford, California 94304, USA.
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MeSH Terms
Angiogenesis Inducing Agents / metabolism
Aorta, Thoracic / physiology
Blood Pressure / physiology
Cardiomegaly / etiology,  genetics,  physiopathology*
Constriction, Pathologic / physiopathology
Genome-Wide Association Study
Heart / physiopathology*
Heart Failure / etiology,  physiopathology
Hypertension / complications,  genetics,  physiopathology*
Mice, Knockout
Microarray Analysis
Paraffin Embedding
RNA / biosynthesis,  genetics
Receptors, Adrenergic, beta / genetics,  physiology*
Receptors, Adrenergic, beta-1 / genetics,  physiology
Receptors, Adrenergic, beta-2 / genetics,  physiology
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / genetics,  physiology
Grant Support
Reg. No./Substance:
0/Angiogenesis Inducing Agents; 0/Receptors, Adrenergic, beta; 0/Receptors, Adrenergic, beta-1; 0/Receptors, Adrenergic, beta-2; 63231-63-0/RNA

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