Cardioprotective mIGF-1/SIRT1 signaling induces hypertension, leukocytosis and fear response in mice.
Locally acting insulin growth factor isoform (mIGF-1) and the NAD+-dependent protein deacetylase SIRT1 are implicated in life and health span. Heart failure is associated with aging and is a major cause of death. mIGF-1 protects the heart from oxidative stresses via SIRT1. SIRT1 subcellular localization and its genomic regulation by mIGF-1 are unknown. We show here that SIRT1 is located in the nuclei of a significant fraction of cardiomyocytes. Using high throughput sequencing approaches in mIGF-1 transgenic mice, we identified new targets of the mIGF-1/SIRT1 signaling. In addition to its potent cardioprotective properties, cardiac-restricted mIGF-1 transgene induced systemic changes such as high blood pressure, leukocytosis and an enhanced fear response, in a SIRT1-dependent manner. Cardiac mIGF-1/ SIRT1 signaling may thus modulate disparate systemic functions.
European Molecular Biology Laboratory (EMBL)-Mouse Biology Unit, Monterotondo, Italy.
Giulia
G
Bolasco
Raffaele
R
Calogero
Matteo
M
Carrara
Mumna Al
MA
Banchaabouchi
Daniel
D
Bilbao
Gianluigi
G
Mazzoccoli
Manlio
M
Vinciguerra
D000818:Animals; D002316:Cardiotonic Agents; D005239:Fear; D006333:Heart Failure / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D007964:Leukocytosis / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac; D018384:Oxidative Stress / Q000502:physiology; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*
D002316:Cardiotonic Agents; D007334:Insulin-Like Growth Factor I; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1