University Hospital Düsseldorf, Medical Faculty, Division of Cardiology, Pulmonology and Vascular Medicine, Moorenstraße 5, 40225 Düsseldorf, Germany.
Biological and Medical Research Center (BMFZ), Heinrich-Heine-University, Universitätsstraße 1, 40225 Düsseldorf, Germany.
Mech Ageing Dev. 2014 Jan;135:15-23. doi: 10.1016/j.mad.2014.01.001. Epub 2014 Jan 18.
Increasing age involves a number of detrimental changes in the cardiovascular system and particularly on the large arteries. It deteriorates vascular integrity and leads to increased vascular stiffness entailing hypertension with increased cardiovascular morbidity and mortality. The consequences of continuous oxidative stress and damages to biomolecules include altered gene expression, genomic instability, mutations, loss of cell division and cellular responses to increased stress. Many studies have been performed in aged C57BL/6 mice; however, analyses of the age-related changes that occur at a gene expression level and transcriptional profile in vascular tissue have not been elucidated in depth. To determine the changes of the vascular transcriptome, we conducted gene expression microarray experiments on aortas of adult and old mice, in which age-related vascular dysfunction was confirmed by increased stiffness and associated systolic hypertension. Our results highlight differentially expressed genes overrepresented in Gene Ontology categories. Molecular interaction and reaction pathways involved in vascular functions and disease, within the transforming growth factor-beta (TGF-β) pathway, the renin-angiotensin system and the detoxification systems are displayed. Our results provide insight to an altered gene expression profile related to age, thus offering useful clues to counteract or prevent vascular aging and its detrimental consequences.
随着年龄的增长，心血管系统会发生许多不利变化，尤其是大动脉。它会损害血管完整性，导致血管僵硬，进而导致高血压，增加心血管发病率和死亡率。持续的氧化应激和生物分子损伤的后果包括改变基因表达、基因组不稳定性、突变、细胞分裂丧失以及细胞对增加的应激的反应。已经在老年 C57BL/6 小鼠中进行了许多研究；然而，在血管组织中，在基因表达水平和转录谱上发生的与年龄相关的变化的分析尚未得到深入阐明。为了确定血管转录组的变化，我们对成年和老年小鼠的主动脉进行了基因表达微阵列实验，其中通过增加的僵硬和相关的收缩压高血压来确认与年龄相关的血管功能障碍。我们的结果突出显示了基因本体论类别中代表性过高的差异表达基因。涉及血管功能和疾病的分子相互作用和反应途径，包括转化生长因子-β（TGF-β）途径、肾素-血管紧张素系统和解毒系统。我们的结果提供了与年龄相关的改变的基因表达谱的深入了解，从而为对抗或预防血管老化及其不利后果提供了有用的线索。
