Effects of RAGE Deletion on the Cardiac Transcriptome during Aging

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.

Shared Proteins and Pathways of Cardiovascular and Cognitive Diseases: Relation to Vascular Cognitive Impairment

“…AGE/RAGE signaling increases OS leading to diabetes mediated vascular calcification. 112 Previous research linked the AGE/RAGE pathway to CD, 113 CVD, 114 and VCI. 115 The link between the Notch pathway to CD, 116 CVD, 117 and VCI 118 are also recognized.…”

Mammalian Diaphanous1 signalling in neurovascular complications of diabetes

“…When changes in differentially expressed genes (DEGs) were mapped onto the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, the AGE-RAGE signalling pathway in diabetic complications emerged among the pathways that had the most critical implications in the process of development of atherosclerotic plaques in fibroblast populations. Furthermore, in the study to identify the age-associated cardiac gene expression signature induced by RAGE deletion, functional inference analysis of transcriptome in the left ventricle of RageÀ/À and WT mice revealed that RAGE deletion is associated with alterations in the expression of genes related to cardiac remodelling, adaptive immunity, T-cell differentiation and activation, IFN signalling and stress pathways (Scavello et al, 2022).…”