Effects of RAGE Deletion on the Cardiac Transcriptome during Aging

Author:

Scavello FrancescoORCID,Piacentini LucaORCID,Castiglione StefaniaORCID,Zeni Filippo,Macrì Federica,Casaburo Manuel,Vinci Maria CristinaORCID,Colombo Gualtiero I.ORCID,Raucci AngelaORCID

Abstract

Cardiac aging is characterized by increased cardiomyocyte hypertrophy, myocardial stiffness, and fibrosis, which enhance cardiovascular risk. The receptor for advanced glycation end-products (RAGE) is involved in several age-related diseases. RAGE knockout (Rage−/−) mice show an acceleration of cardiac dimension changes and interstitial fibrosis with aging. This study identifies the age-associated cardiac gene expression signature induced by RAGE deletion. We analyzed the left ventricle transcriptome of 2.5-(Young), 12-(Middle age, MA), and 21-(Old) months-old female Rage−/− and C57BL/6N (WT) mice. By comparing Young, MA, and Old Rage−/− versus age-matched WT mice, we identified 122, 192, and 12 differently expressed genes, respectively. Functional inference analysis showed that RAGE deletion is associated with: (i) down-regulation of genes involved in antigen processing and presentation of exogenous antigen, adaptive immune response, and cellular responses to interferon beta and gamma in Young animals; (ii) up-regulation of genes related to fatty acid oxidation, cardiac structure remodeling and cellular response to hypoxia in MA mice; (iii) up-regulation of few genes belonging to complement activation and triglyceride biosynthetic process in Old animals. Our findings show that the age-dependent cardiac phenotype of Rage−/− mice is associated with alterations of genes related to adaptive immunity and cardiac stress pathways.

Funder

Fondazione Veronesi

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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