Transcriptomics of post-stroke angiogenesis in the aged brain.
Transcriptomics of post-stroke angiogenesis in the aged brain.
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DOI：
10.3389/fnagi.2014.00044
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发表时间：
2014
影响因子：
4.8
通讯作者：
Popa-Wagner A
中科院分区：
文献类型：
--
作者：
Buga AM;Margaritescu C;Scholz CJ;Radu E;Zelenak C;Popa-Wagner A
尽管中风后血管生成在老年受试者中具有明显的临床意义，但尚未在老年实验模型中对中风后血管生成进行详细的转录组学分析。在这项研究中，通过结合中风转录组学与免疫组化在老年大鼠和中风后患者，我们试图确定一个年龄特异性的基因表达模式，可以表征中风后的血管生成过程。我们发现年轻和年老的梗塞大鼠都启动了旺盛的血管生成。然而，年轻的大鼠在中风后第14天具有更高的血管密度。与年轻动物中血管密度增加相关的“新中风”基因包括Angpt 2、Angptl 2、Angptl 4、Cib 1、Ccr 2、Col 4a 2、Cxcl 1、Lef 1、Hhex、Lamc 1、Nid 2、Pcam 1、Plod 2、Runx 3、Scpep 1、S100 a4、Tgfbi和Wnt 4，它们是萌芽血管生成、基底层（BL）重建和消退期所需的。然而，绝大多数参与出芽血管生成（Angpt 2、Angptl 4、Cib 1、Col 8a 1、Nrp 1、Pcam 1、Pttg 1 ip、Rac 2、Runx 1、Tnp 4、Wnt 4）;新BL的重建（Col 4a 2、Lamc 1、Plod 2）;或管形成和成熟（Angpt 1、Gpc 3、Igfbp 7、Sparc、Tie 2、Tnfsf 10）的基因在老年大鼠中具有延迟的上调。老年大鼠中的血管生成反应因“炎症”基因（Cxcl 12、Mmp 8、Mmp 12、Mmp 14、Mpeg 1、Tnfrsf 1a、Tnfrsf 1b）的持续上调和纤维化瘢痕形成所需基因（Cthrc 1、Il 6 ra、Il 13 ar 1、Il 18、Mmp 2、Rassf 4、Tgfb 1、Tgfbr 2、Timp 1）的强烈表达而进一步减弱。在这个屏障之外，老年大脑中的血管生成与年轻大脑中的血管生成相似。我们还发现，老年人的大脑是能够安装一个有力的血管生成反应中风后，这最有可能反映了剩余的大脑可塑性的老年大脑。
Despite the obvious clinical significance of post-stroke angiogenesis in aged subjects, a detailed transcriptomic analysis of post-stroke angiogenesis has not yet been undertaken in an aged experimental model. In this study, by combining stroke transcriptomics with immunohistochemistry in aged rats and post-stroke patients, we sought to identify an age-specific gene expression pattern that may characterize the angiogenic process after stroke. We found that both young and old infarcted rats initiated vigorous angiogenesis. However, the young rats had a higher vascular density by day 14 post-stroke. “New-for-stroke” genes that were linked to the increased vasculature density in young animals included Angpt2, Angptl2, Angptl4, Cib1, Ccr2, Col4a2, Cxcl1, Lef1, Hhex, Lamc1, Nid2, Pcam1, Plod2, Runx3, Scpep1, S100a4, Tgfbi, and Wnt4, which are required for sprouting angiogenesis, reconstruction of the basal lamina (BL), and the resolution phase. The vast majority of genes involved in sprouting angiogenesis (Angpt2, Angptl4, Cib1, Col8a1, Nrp1, Pcam1, Pttg1ip, Rac2, Runx1, Tnp4, Wnt4); reconstruction of a new BL (Col4a2, Lamc1, Plod2); or tube formation and maturation (Angpt1, Gpc3, Igfbp7, Sparc, Tie2, Tnfsf10), had however, a delayed upregulation in the aged rats. The angiogenic response in aged rats was further diminished by the persistent upregulation of “inflammatory” genes (Cxcl12, Mmp8, Mmp12, Mmp14, Mpeg1, Tnfrsf1a, Tnfrsf1b) and vigorous expression of genes required for the buildup of the fibrotic scar (Cthrc1, Il6ra, Il13ar1, Il18, Mmp2, Rassf4, Tgfb1, Tgfbr2, Timp1). Beyond this barrier, angiogenesis in the aged brains was similar to that in young brains. We also found that the aged human brain is capable of mounting a vigorous angiogenic response after stroke, which most likely reflects the remaining brain plasticity of the aged brain.