Exploring Cardiomyocyte Transcriptome Dynamics: Integrating Human and Rat Data to Understand Aging and Cardiovascular Diseases

ABSTRACT: Cardiovascular diseases including heart failure (HF) are the leading cause of mortality and morbidity. While age is their greatest risk factor, it is not sufficient for HF development. Cardiac remodeling during aging and disease overlap at the structural and functional level with increased fibrosis, cardiomyocyte hypertrophy, and decreased contractility detected. The extent of this overlap and the unique molecular changes that occur with age and pathology in CM are however not established but their identification could provide insight into the mechanisms that underlie the reduced resilience of the aged heart. To these ends, we integrated single nucleus RNA-Seq data of different cardiomyopathies and from young and aged patient samples and probed this data for unique and overlapping features. We further compared with highly phenotyped rat models of aging and pressure overload to mitigate against comorbidities and test the utility of these models for analysis of human aging and disease. In both rats and humans, we identified diverse CM subtypes that changed in their relative abundance with age and pathology. These CM exhibited substantial transcriptomic changes according to age or etiology as well as showing increased cellular and transcriptional heterogeneity. Nodal regulators of these transcriptional changes were identified. While rats showed substantial differences with humans, overlapping features were also detected including increased heterogeneity between CM and changes in specific genes.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE284247 | GEO | 2026/09/14

REPOSITORIES: GEO