Local IGF-1 isoform protects cardiomyocytes from hypertrophic and oxidative stresses via SirT1 activity
Author(s)
Vinciguerra, Manlio
Santini, Maria Paola
Claycomb, William C
Ladurner, Andreas G
Rosenthal, Nadia
Type
Journal Article
Abstract
Oxidative and hypertrophic stresses contribute to the pathogenesis of heart failure. Insulin-like growth factor-1 (IGF-1) is a peptide hormone with a complex post-transcriptional regulation, generating distinct isoforms. Locally acting IGF-1 isoform (mIGF-1) helps the heart to recover from toxic injury and from infarct. In the murine heart, moderate overexpression of the NAD+-dependent deacetylase SirT1 was reported to mitigate oxidative stress. SirT1 is known to promote lifespan extension and to protect from metabolic challenges. Circulating IGF-1 and SirT1 play antagonizing biological roles and share molecular targets in the heart, in turn affecting cardiomyocyte physiology. However, how different IGF-1 isoforms may impact SirT1 and affect cardiomyocyte function is unknown. Here we show that locally acting mIGF-1 increases SirT1 expression/activity, whereas circulating IGF-1 isoform does not affect it, in cultured HL-1 and neonatal cardiomyocytes. mIGF-1-induced SirT1 activity exerts protection against angiotensin II (Ang II)-triggered hypertrophy and against paraquat (PQ) and Ang II-induced oxidative stress. Conversely, circulating IGF-1 triggered itself oxidative stress and cardiomyocyte hypertrophy. Interestingly, potent cardio-protective genes (adiponectin, UCP-1 and MT-2) were increased specifically in mIGF-1-overexpressing cardiomyocytes, in a SirT1-dependent fashion. Thus, mIGF-1 protects cardiomyocytes from oxidative and hypertrophic stresses via SirT1 activity, and may represent a promising cardiac therapeutic.
Date Issued
2010-01-01
Date Acceptance
2009-12-09
Citation
AGING-US, 2010, 2 (1), pp.43-62
ISSN
1945-4589
Publisher
IMPACT JOURNALS LLC
Start Page
43
End Page
62
Journal / Book Title
AGING-US
Volume
2
Issue
1
Copyright Statement
© Vinciguerra et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source
are credited
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source
are credited
License URL
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000276403300005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell Biology
Geriatrics & Gerontology
IGF-1
SirT1
oxidative stress
cell hypertrophy
cardiomyocytes
GROWTH-FACTOR-I
INDUCED CARDIAC-HYPERTROPHY
ANGIOTENSIN-II
TRANSGENIC MICE
HEART-FAILURE
CARDIOVASCULAR-DISEASE
GENE-EXPRESSION
CELL-SURVIVAL
ACTIVATION
MUSCLE
Publication Status
Published
Date Publish Online
2009-12-10