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 are comprised 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.
Highlights
Chronic kidney disease-induced valvular calcification was demonstrated to be slowed by administration of endothelin type A (ETA) receptor atransentan (10 mg/kg/day) which reduced SMC differentiation, calcification, and stiffness [81]
An Italian group discussed the potential use of miRNAs for mitral valve diseases
This process leads to calcification or myxomatous degeneration of cardiac valves and a preventive diagnosis based on miRNA might establish a pharmacological therapeutic target or a basis to improve existing prosthetic devices and treatment options [113,114,115]
Summary
Plasma levels of miRNAs have been used to monitor degenerative disease of the mitral valve (MV) but have not been widely adopted by the cardiology community [4,6,7,9,10,11]. Pathoanatomic features arise because of excessive tissue formation on mitral valve leaflets leading to Barlow’s syndrome [22] while pathoanatomic lesions in older patients tend to manifest as fibroelastic degeneration. Both forms of the disease can lead to leaflet prolapse and chordal elongation or rupture [23,24,25]. The investigators have recorded higher levels of haptoglobin, platelet basic protein, and complement component C4b in individuals with degenerative mitral valve prolapse, the evidence was not conclusive for a specific correlation between biomarkers and disease development [16]. Pathophysiology of Valvular Calcification Pathways, from Preclinical Models to Clinical Perspectives
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