Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA.
Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA.
Aging (Albany NY). 2020 Aug 15;12(15):15603-15623. doi: 10.18632/aging.103652.
Vascular aging has been documented as a vital process leading to arterial dysfunction and age-related cardiovascular and cerebrovascular diseases. However, our understanding of the molecular underpinnings of age-related phenotypes in the vascular system is incomplete. Here we performed bulk RNA sequencing in young and old mouse aortae to elucidate age-associated changes in the transcriptome. Results showed that the majority of upregulated pathways in aged aortae relate to immune response, including inflammation activation, apoptotic clearance, and phagocytosis. The top downregulated pathway in aged aortae was extracellular matrix organization. Additionally, protein folding control and stress response pathways were downregulated in the aged vessels, with an array of downregulated genes encoding heat shock proteins (HSPs). We also found that circadian core clock genes were differentially expressed in young versus old aortae. Finally, transcriptome analysis combined with protein expression examination and smooth muscle cell (SMC) lineage tracing revealed that SMCs in aged aortae retained the differentiated phenotype, with an insignificant decrease in SMC marker gene expression. Our results therefore unveiled critical pathways regulated by arterial aging in mice, which will provide important insight into strategies to defy vascular aging and age-associated vascular diseases.
血管衰老被认为是导致动脉功能障碍和与年龄相关的心血管和脑血管疾病的重要过程。然而，我们对于血管系统中与年龄相关表型的分子基础的理解还不完整。在这里，我们对年轻和年老小鼠的主动脉进行了 bulk RNA 测序，以阐明转录组与年龄相关的变化。结果表明，衰老主动脉中上调途径的大多数与免疫反应有关，包括炎症激活、凋亡清除和吞噬作用。衰老主动脉中下调最明显的途径是细胞外基质组织。此外，蛋白质折叠控制和应激反应途径在衰老血管中下调，许多下调的基因编码热休克蛋白 (HSP)。我们还发现，昼夜节律核心时钟基因在年轻和年老主动脉中的表达存在差异。最后，转录组分析结合蛋白质表达检测和平滑肌细胞 (SMC) 谱系追踪表明，衰老主动脉中的 SMC 保留了分化表型，SMC 标记基因的表达没有明显下降。因此，我们的研究结果揭示了小鼠动脉衰老调控的关键途径，这将为对抗血管衰老和与年龄相关的血管疾病的策略提供重要的见解。
