Effects of MicroRNAs in Valvular Heart Diseases: From Molecular Pathways to Clinical Effects and Therapeutical Strategies

Micro-RNAs have been recently investigated in preclinical and clinical research as regulators of valvulopathies pathogenesis, diagnostic biomarkers and therapeutical targets. Evidences from in-vivo and in-vitro studies demonstrated stimulatory or inhibitory roles in mitral valve prolapse, aortic leaflet fusion and calcification pathways, specifically osteoblastic differentiation and transcription factors modulation. Tissue expression assessment and comparison between physiological and pathological phenotypes or different disease entities, including mitral valve prolapse and mitral chordae tendineae rupture, emerged as the best strategies to address mi-RNAs over or under-representation. In this review we discuss the fundamental intracellular homeostatic and cardiogenetic pathways regulated by mi-RNAs leading to defects in mitral and aortic valves, congenital heart diseases and the possible therapeutical strategies targeting them. Mi-RNAs inhibitors comprise antisense oligonucleotides and sponge vectors while mi-RNA mimics, mi-RNA expression vectors and small molecules are possible practical strategies to increase their activity. Advantages and technical limitations, including instability and complex pharmacokinetics are also presented. Novel strategies, such as nanoparticles and liposomes, are conclusively described to improve knowledge on these molecules delivery and establish future personalized treatment directions.