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Review

An Emerging Role for isomiRs and the microRNA Epitranscriptome in Neovascularization

by
Reginald V.C.T. van der Kwast
1,
Paul H.A. Quax
1 and
A. Yaël Nossent
1,2,*
1
Department of Surgery and Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
2
Department of Laboratory Medicine and Department of Internal Medicine II, Medical University of Vienna, 1090 Vienna, Austria
*
Author to whom correspondence should be addressed.
Cells 2020, 9(1), 61; https://doi.org/10.3390/cells9010061
Submission received: 29 November 2019 / Revised: 19 December 2019 / Accepted: 21 December 2019 / Published: 25 December 2019
(This article belongs to the Special Issue Arteriogenesis and Therapeutic Neovascularization)

Abstract

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.
Keywords: microRNA; isomiRs; epitranscriptome; neovascularization; angiogenesis; arteriogenesis; A-to-I editing; m6A; RNA modifications; RNA methylation microRNA; isomiRs; epitranscriptome; neovascularization; angiogenesis; arteriogenesis; A-to-I editing; m6A; RNA modifications; RNA methylation

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MDPI and ACS Style

van der Kwast, R.V.C.T.; Quax, P.H.A.; Nossent, A.Y. An Emerging Role for isomiRs and the microRNA Epitranscriptome in Neovascularization. Cells 2020, 9, 61. https://doi.org/10.3390/cells9010061

AMA Style

van der Kwast RVCT, Quax PHA, Nossent AY. An Emerging Role for isomiRs and the microRNA Epitranscriptome in Neovascularization. Cells. 2020; 9(1):61. https://doi.org/10.3390/cells9010061

Chicago/Turabian Style

van der Kwast, Reginald V.C.T., Paul H.A. Quax, and A. Yaël Nossent. 2020. "An Emerging Role for isomiRs and the microRNA Epitranscriptome in Neovascularization" Cells 9, no. 1: 61. https://doi.org/10.3390/cells9010061

APA Style

van der Kwast, R. V. C. T., Quax, P. H. A., & Nossent, A. Y. (2020). An Emerging Role for isomiRs and the microRNA Epitranscriptome in Neovascularization. Cells, 9(1), 61. https://doi.org/10.3390/cells9010061

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