Open AccessCardioprotective mIGF-1/SIRT1 signaling induces hypertension, leukocytosis and fear response in mice
Author(s) -
Giulia Bolasco,
Raffaele Calogero,
Matteo Carrara,
Mumna Al Banchaabouchi,
Daniel Bilbao,
Gianluigi Mazzoccoli,
Manlio Vinciguerra
Publication year - 2012
Publication title -
aging
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.473
H-Index - 90
ISSN - 1945-4589
DOI - 10.18632/aging.100464
Subject(s) - genetically modified mouse , leukocytosis , transgene , nad+ kinase , heart failure , sirtuin 1 , gene isoform , biology , microbiology and biotechnology , signal transduction , medicine , sirtuin , endocrinology , pharmacology , gene , biochemistry , downregulation and upregulation , enzyme
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.