The Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon.
Department of Anesthesiology and Perioperative Medicine, Oregon Health and Science University, Portland, Oregon.
Physiol Genomics. 2021 Jul 1;53(7):295-308. doi: 10.1152/physiolgenomics.00037.2021. Epub 2021 Jun 7.
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.
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起着至关重要的作用，但在许多器官系统中，衰老对这种细胞群体的分子影响仍不清楚。在这项研究中，我们试图确定心脏内皮细胞与年龄相关的转录变化。从年轻（3 个月）和年老（24 个月）C57/BL6 小鼠的心脏、大脑和肾脏中分离出高度富集的内皮细胞（EC）群体，通过批量 RNA 测序对其 RNA 表达进行分析。大约 700 个心脏内皮转录本因年龄而显著不同。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细胞表达的受体发生了平行变化。基因和途径富集分析表明，心脏内皮细胞的与年龄相关的转录反应与源自大脑或肾脏血管床的内皮细胞不同。此外，单细胞分析确定了九个不同的 EC 亚型，并表明在小鼠心脏中，富含 Apelin 受体的亚型随着年龄的增长而减少。最后，我们确定了特定衰老心脏内皮亚型中失调的年龄相关基因。
