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Updated: Nov 2, 2025
Epigenetic Regulation of Cardiac Differentiation of Embryonic Stem Cells and Tissues
Published on: June 3, 2016
Age-dependent transcriptional alterations in cardiac endothelial cells
Uchenna Emechebe1, Jonathan W Nelson1, Nabil J Alkayed1,2
1The Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon.
Insights
Aging significantly alters cardiac endothelial cell gene expression, impacting cardiovascular health. This study reveals distinct age-related molecular changes in heart endothelial cells compared to brain and kidney, identifying specific cell subtypes affected by aging.
Area of Science:
- Cardiovascular Biology
- Aging Research
- Molecular Biology
Background:
- Aging is a primary risk factor for cardiovascular disease.
- Endothelial cells are crucial for cardiovascular function and disease pathogenesis.
- The molecular impact of aging on endothelial cells across different organs is not well understood.
Purpose of the Study:
- To investigate age-associated transcriptional alterations in cardiac endothelial cells.
- To compare these changes with those in endothelial cells from the brain and kidney.
- To identify specific endothelial cell subtypes affected by aging in the heart.
Main Methods:
- Isolation of highly enriched endothelial cells (ECs) from young and aged C57/BL6 mouse hearts, brains, and kidneys.
- Bulk RNA sequencing to profile gene expression.
- Gene set enrichment analysis, receptor-ligand interaction analysis, and single-cell RNA sequencing.
Main Results:
- Approximately 700 cardiac endothelial transcripts showed significant age-related differences.
- Similar patterns of cellular pathway perturbations were observed.
- Age-related transcriptional responses in cardiac ECs were distinct from those in brain and kidney ECs.
- Single-cell analysis revealed nine EC subtypes, with the Apelin Receptor-enriched subtype decreasing with age.
- Specific age-dysregulated genes were identified within aged cardiac endothelial subtypes.
Conclusions:
- Aging induces significant and distinct transcriptional changes in cardiac endothelial cells.
- These age-related alterations involve specific cellular pathways and receptor-ligand interactions.
- The Apelin Receptor-expressing EC subtype is particularly vulnerable to aging in the mouse heart.
- Understanding these age-specific molecular changes is crucial for addressing age-related cardiovascular diseases.
Abstract:
Aging is a significant risk factor for cardiovascular disease. Despite the fact that endothelial cells play critical roles in cardiovascular function and disease, the molecular impact of aging on this cell population in many organ systems remains unknown. In this study, we sought to determine age-associated transcriptional alterations in cardiac endothelial cells. Highly enriched populations of endothelial cells (ECs) isolated from the heart, brain, and kidney of young (3 mo) and aged (24 mo) C57/BL6 mice were profiled for RNA expression via bulk RNA sequencing. Approximately 700 cardiac endothelial transcripts significantly differ by age. Gene set enrichment analysis indicated similar patterns for cellular pathway perturbations. Receptor-ligand comparisons indicated parallel alterations in age-affected circulating factors and cardiac endothelial-expressed receptors. Gene and pathway enrichment analyses show that age-related transcriptional response of cardiac endothelial cells is distinct from that of endothelial cells derived from the brain or kidney vascular bed. Furthermore, single-cell analysis identified nine distinct EC subtypes and shows that the Apelin Receptor-enriched subtype is reduced with age in mouse heart. Finally, we identify age-dysregulated genes in specific aged cardiac endothelial subtypes.
