miR-208b upregulation interferes with calcium handling in HL-1 atrial myocytes: Implications in human chronic atrial fibrillation

MicroRNAs (miR) have considerable potential as therapeutic tools in cardiac diseases. Alterations in atrial miR are involved in the development of atrial fibrillation (AF), but the molecular mechanism underlying their contribution to atrial remodeling in chronic atrial fibrillation (CAF) is only partially understood. Here we used miR array to analyze the miR profile of atrial biopsies from sinus rhythm (SR) and CAF patients. qRT-PCR identified a distinctive CAF-miR signature and described conserved miR-208b upregulation in human and ovine AF atrial tissue. We used bioinformatics analysis to predict genes and signaling pathways as putative miR-208b targets, which highlighted genes from the cardiac muscle gene program and from canonical WNT, gap-junction and Ca2 + signaling networks. Results from analysis of miR-208b-overexpressing HL-1 atrial myocytes and from myocytes isolated from CAF patients showed that aberrant miR-208b levels reduced the expression and function of L-type Ca2 + channel subunits (CACNA1C and CACNB2) as well as the sarcoplasmic reticulum-Ca2 + pump SERCA2. These findings clearly pointed to CAF-specific upregulated miR-208b as an important mediator in Ca2 + handling impairment during atrial remodeling.