Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Transcriptome profiling revealed early vascular smooth muscle cell gene activation following focal ischemic stroke in female rats – comparisons with males

Rehnström, Mimmi LU ; Frederiksen, Simona Denise ; Ansar, Saema LU and Edvinsson, Lars LU (2020) In BMC Genomics 21(1).
Abstract

Background: Women account for 60% of all stroke deaths and are more often permanently disabled than men, despite their higher observed stroke incidence. Considering the clinical population affected by stroke, an obvious drawback is that many pre-clinical and clinical studies only investigate young males. To improve therapeutic translation from bench to bedside, we believe that it is advantageous to include both sexes in experimental models of stroke. The aims of this study were to identify early cerebral vascular responses to ischemic stroke in females, compare the differential gene expression patterns with those seen in males, and identify potential new therapeutic targets. Results: Transient middle cerebral artery occlusion (tMCAO)... (More)

Background: Women account for 60% of all stroke deaths and are more often permanently disabled than men, despite their higher observed stroke incidence. Considering the clinical population affected by stroke, an obvious drawback is that many pre-clinical and clinical studies only investigate young males. To improve therapeutic translation from bench to bedside, we believe that it is advantageous to include both sexes in experimental models of stroke. The aims of this study were to identify early cerebral vascular responses to ischemic stroke in females, compare the differential gene expression patterns with those seen in males, and identify potential new therapeutic targets. Results: Transient middle cerebral artery occlusion (tMCAO) was used to induce stroke in both female and male rats, the middle cerebral arteries (MCAs) were isolated 3 h post reperfusion and RNA was extracted. Affymetrix whole transcriptome expression profiling was performed on female (n = 12) MCAs to reveal differentially expressed genes. In total, 1076 genes had an increased expression and 879 genes a decreased expression in the occluded MCAs as compared with the control MCAs from female rats. An enrichment of genes related to apoptosis, regulation of transcription, protein autophosphorylation, inflammation, oxidative stress, and tissue repair and recovery were seen in the occluded MCA. The high expression genes chosen for qPCR verification (Adamts4, Olr1, JunB, Fosl1, Serpine1, S1pr3, Ccl2 and Socs3) were all shown to be upregulated in the same manner in both females and males after tMCAO (p < 0.05; n = 23). When comparing the differentially expressed genes in female MCAs (occluded and non-occluded) with our previous findings in males after tMCAO, a total of 297 genes overlapped (all groups had 32 genes in common). Conclusions: The cascades of processes initiated in the vasculature following reperfusion are complex. Dynamic gene expression alterations were observed in the occluded MCAs, and to a less pronounced degree in the non-occluded MCAs. Dysregulation of inflammation and blood-brain barrier breakdown are possible pharmacological targets. The sample of genes (< 1% of the differentially expressed genes) validated for this microarray did not reveal any sex differences. However, sex differences might be observed for other gene targets.

(Less)
Please use this url to cite or link to this publication:
author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Endothelial function, Female rats, Focal cerebral ischemia, Gene regulation, Inflammation, mRNA, Pathway analysis, Sex differences, Transcription factors, Transcriptomics
in
BMC Genomics
volume
21
issue
1
article number
883
publisher
BioMed Central (BMC)
external identifiers
  • scopus:85097413911
  • pmid:33297959
ISSN
1471-2164
DOI
10.1186/s12864-020-07295-2
language
English
LU publication?
yes
id
30587ade-1f29-4412-b84a-8a527e170d3f
date added to LUP
2020-12-22 08:44:43
date last changed
2024-06-14 06:12:52
@article{30587ade-1f29-4412-b84a-8a527e170d3f,
  abstract     = {{<p>Background: Women account for 60% of all stroke deaths and are more often permanently disabled than men, despite their higher observed stroke incidence. Considering the clinical population affected by stroke, an obvious drawback is that many pre-clinical and clinical studies only investigate young males. To improve therapeutic translation from bench to bedside, we believe that it is advantageous to include both sexes in experimental models of stroke. The aims of this study were to identify early cerebral vascular responses to ischemic stroke in females, compare the differential gene expression patterns with those seen in males, and identify potential new therapeutic targets. Results: Transient middle cerebral artery occlusion (tMCAO) was used to induce stroke in both female and male rats, the middle cerebral arteries (MCAs) were isolated 3 h post reperfusion and RNA was extracted. Affymetrix whole transcriptome expression profiling was performed on female (n = 12) MCAs to reveal differentially expressed genes. In total, 1076 genes had an increased expression and 879 genes a decreased expression in the occluded MCAs as compared with the control MCAs from female rats. An enrichment of genes related to apoptosis, regulation of transcription, protein autophosphorylation, inflammation, oxidative stress, and tissue repair and recovery were seen in the occluded MCA. The high expression genes chosen for qPCR verification (Adamts4, Olr1, JunB, Fosl1, Serpine1, S1pr3, Ccl2 and Socs3) were all shown to be upregulated in the same manner in both females and males after tMCAO (p &lt; 0.05; n = 23). When comparing the differentially expressed genes in female MCAs (occluded and non-occluded) with our previous findings in males after tMCAO, a total of 297 genes overlapped (all groups had 32 genes in common). Conclusions: The cascades of processes initiated in the vasculature following reperfusion are complex. Dynamic gene expression alterations were observed in the occluded MCAs, and to a less pronounced degree in the non-occluded MCAs. Dysregulation of inflammation and blood-brain barrier breakdown are possible pharmacological targets. The sample of genes (&lt; 1% of the differentially expressed genes) validated for this microarray did not reveal any sex differences. However, sex differences might be observed for other gene targets.</p>}},
  author       = {{Rehnström, Mimmi and Frederiksen, Simona Denise and Ansar, Saema and Edvinsson, Lars}},
  issn         = {{1471-2164}},
  keywords     = {{Endothelial function; Female rats; Focal cerebral ischemia; Gene regulation; Inflammation; mRNA; Pathway analysis; Sex differences; Transcription factors; Transcriptomics}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{BMC Genomics}},
  title        = {{Transcriptome profiling revealed early vascular smooth muscle cell gene activation following focal ischemic stroke in female rats – comparisons with males}},
  url          = {{http://dx.doi.org/10.1186/s12864-020-07295-2}},
  doi          = {{10.1186/s12864-020-07295-2}},
  volume       = {{21}},
  year         = {{2020}},
}