An Emerging Role for isomiRs and the microRNA Epitranscriptome in Neovascularization

Therapeutic neovascularization can facilitate blood flow recovery in patients with ischemic cardiovascular disease, the leading cause of death worldwide. Neovascularization encompasses both angiogenesis, the sprouting of new capillaries from existing vessels, and arteriogenesis, the maturation of pr...

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Main Authors: Reginald V.C.T. van der Kwast, Paul H.A. Quax, A. Yaël Nossent
Format: Article
Language:English
Published: MDPI AG 2019-12-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/9/1/61
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author Reginald V.C.T. van der Kwast
Paul H.A. Quax
A. Yaël Nossent
author_facet Reginald V.C.T. van der Kwast
Paul H.A. Quax
A. Yaël Nossent
author_sort Reginald V.C.T. van der Kwast
collection DOAJ
description Therapeutic neovascularization can facilitate blood flow recovery in patients with ischemic cardiovascular disease, the leading cause of death worldwide. Neovascularization encompasses both angiogenesis, the sprouting of new capillaries from existing vessels, and arteriogenesis, the maturation of preexisting collateral arterioles into fully functional arteries. Both angiogenesis and arteriogenesis are highly multifactorial processes that require a multifactorial regulator to be stimulated simultaneously. MicroRNAs can regulate both angiogenesis and arteriogenesis due to their ability to modulate expression of many genes simultaneously. Recent studies have revealed that many microRNAs have variants with altered terminal sequences, known as isomiRs. Additionally, endogenous microRNAs have been identified that carry biochemically modified nucleotides, revealing a dynamic microRNA epitranscriptome. Both types of microRNA alterations were shown to be dynamically regulated in response to ischemia and are able to influence neovascularization by affecting the microRNA’s biogenesis, or even its silencing activity. Therefore, these novel regulatory layers influence microRNA functioning and could provide new opportunities to stimulate neovascularization. In this review we will highlight the formation and function of isomiRs and various forms of microRNA modifications, and discuss recent findings that demonstrate that both isomiRs and microRNA modifications directly affect neovascularization and vascular remodeling.
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spelling doaj.art-ba4d397756c14290b28e9d93be3bf5b62023-08-02T02:59:55ZengMDPI AGCells2073-44092019-12-01916110.3390/cells9010061cells9010061An Emerging Role for isomiRs and the microRNA Epitranscriptome in NeovascularizationReginald V.C.T. van der Kwast0Paul H.A. Quax1A. Yaël Nossent2Department of Surgery and Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Surgery and Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Surgery and Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsTherapeutic neovascularization can facilitate blood flow recovery in patients with ischemic cardiovascular disease, the leading cause of death worldwide. Neovascularization encompasses both angiogenesis, the sprouting of new capillaries from existing vessels, and arteriogenesis, the maturation of preexisting collateral arterioles into fully functional arteries. Both angiogenesis and arteriogenesis are highly multifactorial processes that require a multifactorial regulator to be stimulated simultaneously. MicroRNAs can regulate both angiogenesis and arteriogenesis due to their ability to modulate expression of many genes simultaneously. Recent studies have revealed that many microRNAs have variants with altered terminal sequences, known as isomiRs. Additionally, endogenous microRNAs have been identified that carry biochemically modified nucleotides, revealing a dynamic microRNA epitranscriptome. Both types of microRNA alterations were shown to be dynamically regulated in response to ischemia and are able to influence neovascularization by affecting the microRNA’s biogenesis, or even its silencing activity. Therefore, these novel regulatory layers influence microRNA functioning and could provide new opportunities to stimulate neovascularization. In this review we will highlight the formation and function of isomiRs and various forms of microRNA modifications, and discuss recent findings that demonstrate that both isomiRs and microRNA modifications directly affect neovascularization and vascular remodeling.https://www.mdpi.com/2073-4409/9/1/61micrornaisomirsepitranscriptomeneovascularizationangiogenesisarteriogenesisa-to-i editingm6arna modificationsrna methylation
spellingShingle Reginald V.C.T. van der Kwast
Paul H.A. Quax
A. Yaël Nossent
An Emerging Role for isomiRs and the microRNA Epitranscriptome in Neovascularization
Cells
microrna
isomirs
epitranscriptome
neovascularization
angiogenesis
arteriogenesis
a-to-i editing
m6a
rna modifications
rna methylation
title An Emerging Role for isomiRs and the microRNA Epitranscriptome in Neovascularization
title_full An Emerging Role for isomiRs and the microRNA Epitranscriptome in Neovascularization
title_fullStr An Emerging Role for isomiRs and the microRNA Epitranscriptome in Neovascularization
title_full_unstemmed An Emerging Role for isomiRs and the microRNA Epitranscriptome in Neovascularization
title_short An Emerging Role for isomiRs and the microRNA Epitranscriptome in Neovascularization
title_sort emerging role for isomirs and the microrna epitranscriptome in neovascularization
topic microrna
isomirs
epitranscriptome
neovascularization
angiogenesis
arteriogenesis
a-to-i editing
m6a
rna modifications
rna methylation
url https://www.mdpi.com/2073-4409/9/1/61
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