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

Grell, Anne Sofie; Mostajeran, Maryam; Frederiksen, Simona Denise; Edvinsson, Lars; Ansar, Saema

doi:10.1016/j.neuroscience.2017.10.036

Cited by 8 publications

(18 citation statements)

References 49 publications

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“…Olr1 and Ccl2 expression have earlier been shown to be upregulated in cerebral arteries following tMCAO in both normotensive and hypertensive male rats [20]. Here, we report that this occurs equally well in male and female MCAs after experimental stroke.…”

Section: Discussionsupporting

confidence: 66%

“…The comparison with ndings presented by Grell et al [20] revealed overlap between the differential expressed genes identi ed in the occluded versus non-occluded MCA from Wistar Kyoto (WKY) male rats, the occluded MCA versus non-stroke control arteries from Wistar female rats and the non-occluded MCA versus non-stroke control arteries from Wistar female rats. Thirty-two genes were differentially expressed in each of the experimental groups (Fig.…”

Section: Cross-analysis To Reveal Sex Similaritiesmentioning

confidence: 68%

“…MCAs from females (current study) with MCAs from males (previous study, Grell et al [20]) after tMCAO to contribute to basic knowledge of vascular wall processes in both sexes after stroke.…”

Section: Introductionmentioning

confidence: 72%

“…8). Thirty-two differentially expressed genes found for each of the following experimental stroke groups (tMCAO [transient middle cerebral artery occlusion] stroke models): Occluded versus non-occluded middle cerebral artery (MCA) from Wistar-Kyoto (WKY) male rats (results from Grell et al [20]), (ii) occluded MCA vs nonstroke control arteries from Wistar female rats, and (iii) non-occluded MCA vs non-stroke control arteries from Wistar female rats. The number of overlapping genes can be found in Fig.…”

Section: Cross-analysis To Reveal Sex Similaritiesmentioning

confidence: 99%

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Transcriptome Profiling Revealed Early Vascular Smooth Muscle Cell Gene Activation Following Focal Ischemic Stroke in Female Rats – Comparisons with Males

Rehnström¹,

Frederiksen

Edvinsson³

2020

Preprint

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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 hours post reperfusion and RNA was extracted. Affymetrix whole transcriptome expression profiling was performed on female MCAs to reveal differentially expressed genes. In total, 1076 genes had an increased expression and 879 genes a decreased expression in the occluded MCA as compared to the non-stroke control arteries 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). 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 MCA, and to a less pronounced degree in the non-occluded MCA. 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.

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Section: Discussionsupporting

confidence: 66%

Section: Cross-analysis To Reveal Sex Similaritiesmentioning

confidence: 68%

Section: Introductionmentioning

confidence: 72%

Section: Cross-analysis To Reveal Sex Similaritiesmentioning

confidence: 99%

See 2 more Smart Citations

Transcriptome Profiling Revealed Early Vascular Smooth Muscle Cell Gene Activation Following Focal Ischemic Stroke in Female Rats – Comparisons with Males

Rehnström¹,

Frederiksen

Edvinsson³

2020

Preprint

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“…This is known as ischemia-reperfusion injury [21]. We have previously demonstrated an increased endothelin 1 gene expression in ischemic cerebral arteries from hypertensive rats [22]. Endothelin 1-induced contraction of endothelin A receptors in the ischemic cerebral arteries from hypertensive rats could lead to decreased blood flow to the ischemic area and thereby be one of the injurious mechanisms in ischemia-reperfusion.…”

Section: Discussionmentioning

confidence: 99%

Contractile Responses in Spontaneously Hypertensive Rats after Transient Middle Cerebral Artery Occlusion

et al. 2017

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Stroke is one of the leading causes of mortality and morbidity worldwide, and few therapeutic treatments have shown beneficial effect clinically. One reason for this could be the lack of risk factors incorporated into the preclinical stroke research. We have previously demonstrated phenotypic receptor changes to be one of the injurious mechanisms occurring after stroke but mostly in healthy rats. The aim of this study was to investigate if hypertension has an effect on vasoconstrictive receptor responses to endothelin 1, sarafotoxin 6c and angiotensin II after stroke by inducing transient middle cerebral artery occlusion in spontaneously hypertensive rats and Wistar-Kyoto rats using the wire-myograph. We demonstrated an increased contractile response to endothelin 1 and extracellular potassium as well as an increased carbachol-induced dilator response in the middle cerebral arteries from hypertensive rats after stroke. This study demonstrates the importance of including risk factors in experimental stroke research.

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Renin–Angiotensin–Aldosterone System and LOX-1 Interaction in Hypertension with a Focus on Modulation of the Immune System

Cheng

Shao²,

Mehta³

et al. 2023

The Renin Angiotensin System in Cardiovascular Disease

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

Cited by 8 publications

References 49 publications

Transcriptome Profiling Revealed Early Vascular Smooth Muscle Cell Gene Activation Following Focal Ischemic Stroke in Female Rats – Comparisons with Males

Transcriptome Profiling Revealed Early Vascular Smooth Muscle Cell Gene Activation Following Focal Ischemic Stroke in Female Rats – Comparisons with Males

Contractile Responses in Spontaneously Hypertensive Rats after Transient Middle Cerebral Artery Occlusion

Renin–Angiotensin–Aldosterone System and LOX-1 Interaction in Hypertension with a Focus on Modulation of the Immune System

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