Sex differences in intracranial and extracranial atherosclerosis in patients with acute ischemic stroke

Voigt, Sabine; Os, Hja van; Walderveen, Maa van; Schaaf, Irene C. van der; Kappelle, L. Jaap; Broersen, Alexander; Velthuis, BK; Jong, Pa de; Kockelkoren, Remko; Kruyt, N.D.; Algra, Ale; Wermer, M.J.H.

doi:10.1177/1747493020932806

Cited by 19 publications

(15 citation statements)

References 16 publications

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“…However, the coeffect of rs3130685-rs2222896-drinking increased CAD risk, here, the mutation of genes was the dominant factor for increasing risk of CAD. Smoking is an independent risk factor for accelerating atherosclerosis ( Taskinen and Borén, 2015 ; Voigt et al, 2020 ). However, in this study, it showed that minimal smoking independently reduced the risk of IS, and the synergy of minimal smoking with haplotype H1 significantly reduced the risk of IS.…”

Section: Discussionmentioning

confidence: 99%

EHBP1, TUBB, and WWOX SNPs, Gene-Gene and Gene-Environment Interactions on Coronary Artery Disease and Ischemic Stroke

et al. 2022

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The associations among the EH domain-binding protein 1 (EHBP1), tubulin beta class I (TUBB), and WW domain-containing oxidoreductase (WWOX) single nucleotide polymorphisms (SNPs) and coronary artery disease (CAD) and ischemic stroke (IS) are not yet understood. This study aimed to detect the associations of these SNPs, gene-gene and gene-environment interactions and CAD and IS in the Guangxi Han population. A total of 1853 unrelated subjects were recruited into normal control (n = 638), CAD (n = 622), and IS (n = 593) groups. Related genotypes were determined by high-throughput sequencing. The genotypic and minor allelic frequencies of rs2278075 were different between the CAD and control groups, and those of rs2710642, rs3130685, and rs2278075 were also different between the IS and control groups. The rs2278075T allele, rs3130685-rs2222896-rs2278075, rs3130685-rs2222896-diabetes, rs3130685-rs2222896-drinking, and haplotype rs2710642A-rs10496099C-diabetes interactions were associated with increased risk, while G-T-G-C-G-A and G-T-T-T-G-T-drinking were associated with reduced risk of CAD. The rs2278075T and rs2710642G alleles, rs2710642G-rs10496099C haplotype, rs3130685-rs2278075-rs2222896, and rs2710642-rs2278075-hypertension interactions aggravated the association with IS, whereas the rs3130685T allele, rs2710642A-rs10496099C haplotype and the interactions of H1 (s2710642A-rs10496099C)-H2 (rs2710642G-rs10496099C)-drinking and I1 (A-C-G-C-A-A)-I3 (A-C-G-T-A-A)-I4 (A-C-G-T-G-A)-I5 (G-T-G-C-G-A) diminished the association with IS. Carrying WWOX rs2278075T was strongly associated with CAD or IS, while EHBP1 rs2710642 and TUBB rs3130685 might alter the association of IS by modifying the serum lipid profile. This study demonstrates that the EHBP1, TUBB, and WWOX SNPs, gene-gene and gene-environment interactions are associated with the risk of CAD and IS in the Guangxi Han population.

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Section: Discussionmentioning

confidence: 99%

EHBP1, TUBB, and WWOX SNPs, Gene-Gene and Gene-Environment Interactions on Coronary Artery Disease and Ischemic Stroke

et al. 2022

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“…In summary, these studies demonstrate that following carotid artery atherosclerosis, the expression of particular X-linked microRNAs (i.e., miR-188, miR-362, miR-503, miR-532, miR-542) is decreased and promotes VSMC proliferation. Although gene expression results in these studies were not stratified for women and men, these findings could provide a novel molecular mechanism for sex-specific atherosclerotic phenotypes given that extracranial atherosclerosis is less often present in women compared to men [ 74 ].…”

Section: Stroke Promoting Mechanismsmentioning

confidence: 99%

Sex-Specific MicroRNAs in Neurovascular Units in Ischemic Stroke

Florijn

Bijkerk

Kruyt

et al. 2021

IJMS

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Accumulating evidence pinpoints sex differences in stroke incidence, etiology and outcome. Therefore, more understanding of the sex-specific mechanisms that lead to ischemic stroke and aggravation of secondary damage after stroke is needed. Our current mechanistic understanding of cerebral ischemia states that endothelial quiescence in neurovascular units (NVUs) is a major physiological parameter affecting the cellular response to neuron, astrocyte and vascular smooth muscle cell (VSMC) injury. Although a hallmark of the response to injury in these cells is transcriptional activation, noncoding RNAs such as microRNAs exhibit cell-type and context dependent regulation of gene expression at the post-transcriptional level. This review assesses whether sex-specific microRNA expression (either derived from X-chromosome loci following incomplete X-chromosome inactivation or regulated by estrogen in their biogenesis) in these cells controls NVU quiescence, and as such, could differentiate stroke pathophysiology in women compared to men. Their adverse expression was found to decrease tight junction affinity in endothelial cells and activate VSMC proliferation, while their regulation of paracrine astrocyte signaling was shown to neutralize sex-specific apoptotic pathways in neurons. As such, these microRNAs have cell type-specific functions in astrocytes and vascular cells which act on one another, thereby affecting the cell viability of neurons. Furthermore, these microRNAs display actual and potential clinical implications as diagnostic and prognostic biomarkers in ischemic stroke and in predicting therapeutic response to antiplatelet therapy. In conclusion, this review improves the current mechanistic understanding of the molecular mechanisms leading to ischemic stroke in women and highlights the clinical promise of sex-specific microRNAs as novel diagnostic biomarkers for (silent) ischemic stroke.

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“…A recent study had reported that the association between the increased hypertension severity and the onset of ischemic stroke was almost twice as strong in women as in men ( Madsen et al, 2019 ). In addition, Voigt et al reported that the total and proximal plaque burdens were significantly higher for hypertensive male patients with acute ischemic stroke than for their female counterparts ( Voigt et al, 2021 ). Zhong et al reported that elevated plasma tHcy level predicted the poor prognosis of acute ischemic stroke for women, but not for men ( Zhong et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, Voigt et al reported that the total and proximal plaque burdens were significantly higher for hypertensive male patients with acute ischemic stroke than for their female counterparts (Voigt et al, 2021). Zhong et al reported that elevated plasma tHcy level predicted the poor prognosis of acute ischemic stroke for women, but not for men (Zhong et al, 2017).…”

Section: Dependent Variablesmentioning

confidence: 99%

Gender difference in association between H-type hypertension and subcortical ischemic vascular disease

Wang

Xi²,

Li³

et al. 2022

Front. Aging Neurosci.

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BackgroundSubcortical ischemic vascular disease (SIVD) is a leading cause of vascular dementia. The present study tries to explore not only the gender-specific association between H-type hypertension and SIVD but also the indirect effects of H-type hypertension on cognition through the ischemic brain injury caused by SIVD.Materials and methodsA total of 601 SIVD patients were included, comprising 322 males and 279 females. H-type hypertension was defined as hypertension accompanied with elevated serum total homocysteine (tHcy) level. The imaging manifestations of ischemic brain injury caused by SIVD were also evaluated, including white matter lesions (WML), lacunar infarction (LI) and brain atrophy (BA). Gender-specific subgroup analyses in association between H-type hypertension and SIVD were conducted, followed by a structural equation model based evaluation of the gender-specific mediating effects of SIVD on the relationship between H-type hypertension and cognition.ResultsFor males, there was no noticeable difference in WML, LI and BA scores among control group, isolated hypertension group, isolated high tHcy group, and H-type hypertension group in most brain regions, but significant difference was found in all brain regions for females. Multiple regression analyses showed that H-type hypertension was significantly associated with WML, LI and BA for females, but not for males. For males, H-type hypertension mainly affected cognition through direct effect, while the H-type hypertension effect was mediated by ischemic brain injury caused by SIVD for females.ConclusionH-type hypertension was more closely related to SIVD for females than males, suggesting a gender-specific difference in association patterns between H-type hypertension and cognition.

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Sex differences in intracranial and extracranial atherosclerosis in patients with acute ischemic stroke

Cited by 19 publications

References 16 publications

EHBP1, TUBB, and WWOX SNPs, Gene-Gene and Gene-Environment Interactions on Coronary Artery Disease and Ischemic Stroke

EHBP1, TUBB, and WWOX SNPs, Gene-Gene and Gene-Environment Interactions on Coronary Artery Disease and Ischemic Stroke

Sex-Specific MicroRNAs in Neurovascular Units in Ischemic Stroke

Gender difference in association between H-type hypertension and subcortical ischemic vascular disease

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