Preprint Review Version 2 Preserved in Portico This version is not peer-reviewed

MicroRNAs in Valvular Heart Diseases: Biological Regulators, Prognostic Markers and Therapeutical Targets

Version 1 : Received: 14 July 2021 / Approved: 16 July 2021 / Online: 16 July 2021 (15:26:09 CEST)
Version 2 : Received: 4 November 2021 / Approved: 8 November 2021 / Online: 8 November 2021 (14:25:40 CET)

How to cite: Nappi, F.; Iervolino, A.; Avtaar Singh, S.S.; Chello, M. MicroRNAs in Valvular Heart Diseases: Biological Regulators, Prognostic Markers and Therapeutical Targets. Preprints 2021, 2021070384 (doi: 10.20944/preprints202107.0384.v2). Nappi, F.; Iervolino, A.; Avtaar Singh, S.S.; Chello, M. MicroRNAs in Valvular Heart Diseases: Biological Regulators, Prognostic Markers and Therapeutical Targets. Preprints 2021, 2021070384 (doi: 10.20944/preprints202107.0384.v2).

Abstract

miRNAs have recently attracted investigators' interest as regulators of valvular diseases pathogenesis, diagnostic biomarkers, and therapeutical targets. Evidence from in-vivo and in-vitro studies demonstrated stimulatory or inhibitory roles in mitral valve prolapse development, aortic leaflet fusion, and calcification pathways, specifically osteoblastic differentiation and transcription factors modulation. Tissue expression assessment and comparison between physiological and pathological phenotypes of different disease entities, including mitral valve prolapse and mitral chordae tendineae rupture, emerged as the best strategies to address miRNAs over or under-representation and thus, their impact on pathogeneses. In this review, we discuss the fundamental intra- and intercellular signals regulated by miRNAs leading to defects in mitral and aortic valves, congenital heart diseases, and the possible therapeutic strategies targeting them. These miRNAs inhibitors comprise of antisense oligonucleotides and sponge vectors. The miRNA mimics, miRNA expression vectors, and small molecules are instead possible practical strategies to increase specific miRNA activity. Advantages and technical limitations of these new drugs, including instability and complex pharmacokinetics, are also presented. Novel delivery strategies, such as nanoparticles and liposomes, are described to improve knowledge on future personalized treatment directions.

Keywords

miRNAs; valvular heart diseases; aortic stenosis; calcification; mitral valve prolapse, aortic valve defect; vectors; delivery systems; nanoparticles

Subject

MEDICINE & PHARMACOLOGY, Cardiology

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