Sex-Specific MicroRNAs in Neurovascular Units in Ischemic Stroke

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...

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Autores principales:	Barend W. Florijn, Roel Bijkerk, Nyika D. Kruyt, Anton Jan van Zonneveld, Marieke J. H. Wermer
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	microRNA stroke women neurovascular unit Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/74cb79eaad024a478d4d27ff7d0ca746
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spelling	oai:doaj.org-article:74cb79eaad024a478d4d27ff7d0ca7462021-11-11T17:18:33ZSex-Specific MicroRNAs in Neurovascular Units in Ischemic Stroke10.3390/ijms2221118881422-00671661-6596https://doaj.org/article/74cb79eaad024a478d4d27ff7d0ca7462021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11888https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Accumulating 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.Barend W. FlorijnRoel BijkerkNyika D. KruytAnton Jan van ZonneveldMarieke J. H. WermerMDPI AGarticlemicroRNAstrokewomenneurovascular unitBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11888, p 11888 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	microRNA stroke women neurovascular unit Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	microRNA stroke women neurovascular unit Biology (General) QH301-705.5 Chemistry QD1-999 Barend W. Florijn Roel Bijkerk Nyika D. Kruyt Anton Jan van Zonneveld Marieke J. H. Wermer Sex-Specific MicroRNAs in Neurovascular Units in Ischemic Stroke
description	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.
format	article
author	Barend W. Florijn Roel Bijkerk Nyika D. Kruyt Anton Jan van Zonneveld Marieke J. H. Wermer
author_facet	Barend W. Florijn Roel Bijkerk Nyika D. Kruyt Anton Jan van Zonneveld Marieke J. H. Wermer
author_sort	Barend W. Florijn
title	Sex-Specific MicroRNAs in Neurovascular Units in Ischemic Stroke
title_short	Sex-Specific MicroRNAs in Neurovascular Units in Ischemic Stroke
title_full	Sex-Specific MicroRNAs in Neurovascular Units in Ischemic Stroke
title_fullStr	Sex-Specific MicroRNAs in Neurovascular Units in Ischemic Stroke
title_full_unstemmed	Sex-Specific MicroRNAs in Neurovascular Units in Ischemic Stroke
title_sort	sex-specific micrornas in neurovascular units in ischemic stroke
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/74cb79eaad024a478d4d27ff7d0ca746
work_keys_str_mv	AT barendwflorijn sexspecificmicrornasinneurovascularunitsinischemicstroke AT roelbijkerk sexspecificmicrornasinneurovascularunitsinischemicstroke AT nyikadkruyt sexspecificmicrornasinneurovascularunitsinischemicstroke AT antonjanvanzonneveld sexspecificmicrornasinneurovascularunitsinischemicstroke AT mariekejhwermer sexspecificmicrornasinneurovascularunitsinischemicstroke
_version_	1718432124204220416

Sex-Specific MicroRNAs in Neurovascular Units in Ischemic Stroke

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