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Cerebrovascular Gene Expression in Spontaneously Hypertensive Rats After Transient Middle Cerebral Artery Occlusion

Grell, Anne Sofie LU ; Mostajeran, Maryam LU ; Frederiksen, Simona Denise ; Edvinsson, Lars LU and Ansar, Saema LU (2017) In Neuroscience 367. p.219-232
Abstract

Hypertension is a major risk factor for stroke, which is one of the leading global causes of death. In the search for new and effective therapeutic targets in stroke research, we need to understand the influence of hypertension in the vasculature following stroke. We used Affymetrix whole-transcriptome expression profiling as a tool to address gene expression differences between the occluded and non-occluded middle cerebral arteries (MCAs) from spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats after transient middle cerebral artery occlusion (tMCAO), to provide clues about the pathological mechanisms set in play after stroke. Verified by quantitative PCR, expression of Ccl2, Edn1, Tgfβ2, Olr1 and Serpine1... (More)

Hypertension is a major risk factor for stroke, which is one of the leading global causes of death. In the search for new and effective therapeutic targets in stroke research, we need to understand the influence of hypertension in the vasculature following stroke. We used Affymetrix whole-transcriptome expression profiling as a tool to address gene expression differences between the occluded and non-occluded middle cerebral arteries (MCAs) from spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats after transient middle cerebral artery occlusion (tMCAO), to provide clues about the pathological mechanisms set in play after stroke. Verified by quantitative PCR, expression of Ccl2, Edn1, Tgfβ2, Olr1 and Serpine1 was significantly increased in the occluded compared to non-occluded MCAs from both SHRs and WKY rats. Additionally, expression of Mmp9, Icam1, Hif1α and Timp1 was increased in the occluded compared to non-occluded MCAs isolated from WKY rats. In comparison between occluded MCAs from SHRs versus occluded MCAs from WKY rats, expression of Ccl2, Olr1 and Serpine1 was significantly increased in SHR MCAs. However, the opposite was observed regarding expression of Edn1. Thus these data suggest that Ccl2, Edn1, Tgfβ2, Olr1 and Serpine1 may be possible mediators of the vascular changes in the occluded MCAs from both SHRs and WKY rats after tMCAO. The aforementioned genes possess biological functions that are consistent with early stroke injuries. In conclusion, these genes may be potential targets in future strategies for acute stroke treatments that can be used in patients with and without hypertension.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
affymetrix whole-transcriptome expression profiling, gene expression, middle cerebral arteries, spontaneously hypertensive rats, transient middle cerebral artery occlusion
in
Neuroscience
volume
367
pages
14 pages
publisher
Elsevier
external identifiers
  • wos:000417016700021
  • pmid:29102661
  • scopus:85034426369
ISSN
0306-4522
DOI
10.1016/j.neuroscience.2017.10.036
language
English
LU publication?
yes
id
4e3f49ca-eadd-46cd-bf38-c833f9e5d11a
date added to LUP
2017-12-07 12:32:25
date last changed
2024-05-13 02:18:52
@article{4e3f49ca-eadd-46cd-bf38-c833f9e5d11a,
  abstract     = {{<p>Hypertension is a major risk factor for stroke, which is one of the leading global causes of death. In the search for new and effective therapeutic targets in stroke research, we need to understand the influence of hypertension in the vasculature following stroke. We used Affymetrix whole-transcriptome expression profiling as a tool to address gene expression differences between the occluded and non-occluded middle cerebral arteries (MCAs) from spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats after transient middle cerebral artery occlusion (tMCAO), to provide clues about the pathological mechanisms set in play after stroke. Verified by quantitative PCR, expression of Ccl2, Edn1, Tgfβ2, Olr1 and Serpine1 was significantly increased in the occluded compared to non-occluded MCAs from both SHRs and WKY rats. Additionally, expression of Mmp9, Icam1, Hif1α and Timp1 was increased in the occluded compared to non-occluded MCAs isolated from WKY rats. In comparison between occluded MCAs from SHRs versus occluded MCAs from WKY rats, expression of Ccl2, Olr1 and Serpine1 was significantly increased in SHR MCAs. However, the opposite was observed regarding expression of Edn1. Thus these data suggest that Ccl2, Edn1, Tgfβ2, Olr1 and Serpine1 may be possible mediators of the vascular changes in the occluded MCAs from both SHRs and WKY rats after tMCAO. The aforementioned genes possess biological functions that are consistent with early stroke injuries. In conclusion, these genes may be potential targets in future strategies for acute stroke treatments that can be used in patients with and without hypertension.</p>}},
  author       = {{Grell, Anne Sofie and Mostajeran, Maryam and Frederiksen, Simona Denise and Edvinsson, Lars and Ansar, Saema}},
  issn         = {{0306-4522}},
  keywords     = {{affymetrix whole-transcriptome expression profiling; gene expression; middle cerebral arteries; spontaneously hypertensive rats; transient middle cerebral artery occlusion}},
  language     = {{eng}},
  month        = {{12}},
  pages        = {{219--232}},
  publisher    = {{Elsevier}},
  series       = {{Neuroscience}},
  title        = {{Cerebrovascular Gene Expression in Spontaneously Hypertensive Rats After Transient Middle Cerebral Artery Occlusion}},
  url          = {{http://dx.doi.org/10.1016/j.neuroscience.2017.10.036}},
  doi          = {{10.1016/j.neuroscience.2017.10.036}},
  volume       = {{367}},
  year         = {{2017}},
}