10.6084/m9.figshare.1568335.v1 Pauli Ohukainen Pauli Ohukainen Juha Näpänkangas Juha Näpänkangas Kristiina Rajamäki Kristiina Rajamäki Panu Taskinen Panu Taskinen Satu Helske-Suihko Satu Helske-Suihko Petri T. Kovanen Petri T. Kovanen Heikki Ruskoaho Heikki Ruskoaho Jaana Rysä Jaana Rysä Suvi Syväranta Suvi Syväranta Tuomas Peltonen Tuomas Peltonen MicroRNA-125b and chemokine CCL4 expression are associated with calcific aortic valve disease Taylor & Francis Group 2015 thp DNA microarray analysis CCl 4 mRNA expression profiles stenotic aortic valves CAVD control valves CCL 4 gene expression calcific aortic valve disease Calcific aortic valve disease AS valves miRNA target prediction databases chemokine CCL 4 expression 2015-07-04 00:00:00 Journal contribution https://tandf.figshare.com/articles/journal_contribution/MicroRNA_125b_and_chemokine_CCL4_expression_are_associated_with_calcific_aortic_valve_disease/1568335 <div><p></p><p>Calcific aortic valve disease (CAVD) is a progressive pathological condition with no effective pharmacological therapy. To identify novel molecular pathways as potential targets for pharmacotherapy, we studied microRNA (miRNA) profiles of heavily stenotic aortic valves (AS). One of the most upregulated miRNAs in AS valves compared to control valves was miR-125b (1.4-fold; <i>P</i> < 0.05). To identify CAVD-related changes in gene expression, DNA microarray analysis was performed, including an intermediate fibro(sclero)tic stage of the disease. This revealed changes especially in genes related to inflammation and immune response, including chemokine (C-C motif) ligand 3 (CCL3) and 4 (CCL4). CCL3 mRNA level was increased 3.9-fold (<i>P</i> < 0.05) when AS valves were compared to control valves, and a 2.5-fold increase (<i>P</i> < 0.05) in CCL4 gene expression was observed when fibro(sclero)tic valves were compared to control valves. Both CCL3 and CCL4 localized to macrophages by immunofluorescence. To identify chemokine–miRNA target pairs, data from miRNA target prediction databases were combined with valvular miRNA and mRNA expression profiles. MiR-125b was computationally predicted to target CCL4, as confirmed experimentally in cultured human THP-1 macrophages. Collectively, miR-125b and CCL4 appear to be involved in the progression of CAVD and may offer novel therapeutic and diagnostic strategies related to this disease.</p></div>