Effects of aging, hypertension and diabetes on the mouse brain and heart vasculomes.
Effects of aging, hypertension and diabetes on the mouse brain and heart vasculomes.
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DOI：
10.1016/j.nbd.2018.07.021
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发表时间：
2019-06
影响因子：
6.1
通讯作者：
Lo EH
中科院分区：
文献类型：
--
作者：
Guo S;Deng W;Xing C;Zhou Y;Ning M;Lo EH
血管组的新概念表明，微血管有助于每个器官的功能和功能障碍。在大脑中，衰老和合并症（如高血压和糖尿病）显著影响各种神经退行性疾病和脑血管疾病，但其潜在机制很复杂，仍有待充分阐明。在这里，我们假设衰老、高血压和糖尿病扰乱了血管组中的基因网络。从小鼠脑和心脏中分离微血管内皮细胞，并用微阵列分析其转录组。对于衰老，我们比较了5个月与15个月大的C57 BL 6雄性小鼠。对于高血压，我们比较了4月龄血压正常的BPN与高血压BPH雄性小鼠。对于糖尿病，我们比较了3月龄糖尿病db/db小鼠与其匹配的C57 BLKS对照。从这些比较分析中得出了四种总体模式。首先，大脑和心脏之间的器官差异大于年龄和合并症本身的影响。第二，在所有条件下，与心脏相比，脑血管中更多的基因发生了改变。第三，年龄、高血压和糖尿病以不同的方式扰乱大脑和心脏血管，几乎没有重叠。第四，尽管如此，在大脑中检测到了一些常见的途径，主要表现为免疫反应的抑制。这些初步草案的大脑和心脏vasculomes的背景下，老龄化和血管共病应提供一个框架，设计未来的调查，在中枢神经系统疾病的潜在目标和机制。
The emerging concept of the vasculome suggests that microvessels contribute to function and dysfunction in every organ. In the brain, aging and comorbidities such as hypertension and diabetes significantly influence a wide variety of neurodegenerative and cerebrovascular disorders, but the underlying mechanisms are complex and remain to be fully elucidated. Here, we hypothesize that aging, hypertension and diabetes perturb gene networks in the vasculome. Microvascular endothelial cells were isolated from mouse brain and heart, and their transcriptomes were profiled with microarrays. For aging, we compared 5 mo vs 15 mo old C57BL6 male mice. For hypertension, we compared 4 mo old normotensive BPN vs hypertensive BPH male mice. For diabetes, we compared 3 mo old diabetic db/db mice with their matching C57BLKS controls. Four overall patterns arose from these comparative analyses. First, organ differences between brain and heart were larger than effects of age and co-morbidities per se. Second, across all conditions, more genes were altered in the brain vasculome compared with the heart. Third, age, hypertension and diabetes perturbed the brain and heart vasculomes in mostly distinct ways, with little overlap. Fourth, nevertheless, a few common pathways were detected in the brain, expressed mostly as a suppression of immune response. These initial drafts of the brain and heart vasculomes in the context of aging and vascular comorbidities should provide a framework for designing future investigations into potential targets and mechanisms in CNS disease.
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影响因子：
29
作者：
Courties, Gabriel;Moskowitz, Michael A.;Nahrendorf, Matthias
通讯作者：
Nahrendorf, Matthias
影响因子：
8.3
作者：
Ning M;Sarracino DA;Kho AT;Guo S;Lee SR;Krastins B;Buonanno FS;Vizcaíno JA;Orchard S;McMullin D;Wang X;Lo EH
通讯作者：
Lo EH
影响因子：
6.3
作者：
Andersen, Jens V.;Christensen, Sofie K.;Waagepetersen, Helle S.
通讯作者：
Waagepetersen, Helle S.
影响因子：
4.2
作者：
Guo, Shuzhen;Lok, Josephine;Lo, Eng H.
通讯作者：
Lo, Eng H.
影响因子：
6.3
作者：
Lubomirov, Lubomir T.;Papadopoulos, Symeon;Pfitzer, Gabriele
通讯作者：
Pfitzer, Gabriele