Document Detail


IGF1-receptor signalling attenuates the age-related decline of diastolic cardiac function.
MedLine Citation:
PMID:  22589390     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Insulin-like growth factor (IGF1R) signalling has been implicated to play an important role in regulation of cardiac growth, hypertrophy and contractile function, and has been linked to the development of age related congestive heart failure. Here we address the question to what extent cardiomyocyte specific IGF1 signalling is essential for maintenance of the structural and functional integrity of the adult murine heart. To investigate the effects of IGF1 signalling in the adult heart without confounding effects due to IGF1 over-expression or adaptation during embryonic and early post-natal development, we inactivated the IGF1R by a 4-hydroxy tamoxifen inducible Cre recombinase in adult cardiac myocytes. Efficient inactivation of the IGF1R (iCMIGF1RKO) as assessed by Western analysis and real-time PCR went along with reduced IGF1-dependent AKT and GSK3β-phosphorylation. Functional analysis by conductance manometry and magnetic resonance imaging (MRI) revealed no functional alterations in young adult iCMIGF1RKO mice (age 3 month). However, when induced in aged mice (11 month) diastolic cardiac function was depressed. To address the question if insulin signalling might compensate for the defective IGF1R signalling we inactivated β-cells by streptozotocin. However, the diabetes associated functional depression was similar in controls and iCMIGF1RKO mice. Similarly, analysis of the cardiac gene expression profile on 44K microarrays did not reveal activation of overt adaptive processes. Endogenous IGF1 receptor signalling is required for conservation of cardiac function of the aging heart, but not for the integrity of cardiac structure and function of young hearts.
Authors:
Sarah Moellendorf; Claudia Kessels; Lena Peiseler; Annika Raupch; Christoph Jacoby; Nora Vogt; Antje Lindecke; Linda Koch; Jens Bruning; Jacqeuline Heger; Karl Köhrer; Axel Godecke
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-15
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  -     ISSN:  1522-1555     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1Heinrich-Heine-Universität.
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