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Genetic expression and immunofluorescence mapping of NaV1 highlight potential therapeutic targets in anti-inflammatory treatment of aortic valves stenosis

      Background and Aims : Aortic valve stenosis (AVS) is the most prevalent heart valve disease worldwide. Despite better interventional treatment strategies, AVS is associated with a high morbidity and mortality. The aortic valve is innervated, but the neural regulation of these AVS processes is unknown. Recently, a genome wide analysis study (GWAS) associated neuron navigator 1 (NAV1) with AVS. Since NAV1 is a microtubule-associated protein involved in developmental neural migration, the aim of the study was to establish the relation of NAV1 expression to AVS disease stages and AVS pathophysiological pathways, and to map the neural NAV1 to demonstrate its possible role in guiding the valvular anti-inflammatory cholinergic pathway.
      Methods: Human aortic valves were obtained from patients undergoing surgical aortic valve replacement at Karolinska University Hospital in Stockholm (Sweden). The valves were used for (1) RNA extraction and (2) for immunohistochemistry. Gene expression was determined by Affymetrix Human Transcriptome Arrays 2.0 and analysed the statistical software Qlucore (Sweden). NAV1 protein expression was localized and quantified by computerized image analysis from the Light Sheet Microscope (LSM, Scotland).
      Results: In 74 stenotic aortic valves, NAV1 mRNA expression was significantly gradually decreased when disease stages progressed from healthy through intermediate to calcified aortic valve tissue. Immunofluorescence NAV1 staining was in contrast visualized with LSM only in calcified valve tissue.
      Conclusions: These results identified differential valvular NAV1 expression patterns with decreased mRNA and increased protein expression in calcified aortic valve tissue. These results point to NAV1 as a local valvular potential therapeutic target for future studies.