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 months) and aged (24 months) 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. Single-cell RNA-seq analysis identified 9 distinct endothelial cell subtypes in the heart with an age-associated population shift observed for the Aplnr-enriched endothelial cell clusters. 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 9 distinct EC subtypes, and shows that the Aplnr-enriched subtype is reduced with age in mouse heart. Finally, we identify age-dysregulated genes in specific aged cardiac endothelial subtypes.

中文翻译：

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心脏内皮细胞年龄依赖性转录改变


衰老是心血管疾病的一个重要危险因素。尽管内皮细胞在心血管功能和疾病中发挥着关键作用，但衰老对许多器官系统中细胞群的分子影响仍然未知。在这项研究中，我们试图确定心脏内皮细胞中与年龄相关的转录变化。通过批量 RNA 测序，对从年轻（3 个月）和老年（24 个月）C57/BL6 小鼠的心脏、大脑和肾脏中分离出的高度富集的内皮细胞 (EC) 群体进行 RNA 表达分析。大约 700 个心脏内皮转录本因年龄而存在显着差异。基因集富集分析表明细胞通路扰动具有相似的模式。受体-配体比较表明受年龄影响的循环因子和心脏内皮表达受体的平行变化。单细胞 RNA-seq 分析鉴定了心脏中 9 种不同的内皮细胞亚型，在富含 Aplnr 的内皮细胞簇中观察到与年龄相关的群体变化。基因和通路富集分析表明，心脏内皮细胞的年龄相关转录反应与源自脑或肾血管床的内皮细胞的转录反应不同。此外，单细胞分析鉴定了 9 种不同的 EC 亚型，并表明小鼠心脏中富含 Aplnr 的亚型随着年龄的增长而减少。最后，我们确定了特定老年心脏内皮亚型中年龄失调的基因。