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Transcriptomics of Post-Stroke Angiogenesis in the Aged Brain

Please always quote using this URN: urn:nbn:de:bvb:20-opus-120700
  • 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 youngDespite 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.show moreshow less

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Metadaten
Author: Ana Maria Buga, Claudiu Margaritescu, Claus Jürgen Scholz, Eugen Radu, Christine Zelenak, Aurel Popa-Wagner
URN:urn:nbn:de:bvb:20-opus-120700
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Virologie und Immunbiologie
Language:English
Parent Title (English):Frontiers in Aging Neuroscience
Year of Completion:2014
Volume:6
Issue:44
Source:Frontiers in Aging Neuroscience 6:44. doi:10.3389/fnagi.2014.00044
DOI:https://doi.org/10.3389/fnagi.2014.00044
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=24672479
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:aging; angiogenesis; stroke; transcriptomics
Release Date:2016/02/15
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung