Abstract 17711: Human Induced-pluripotent Stem Cell-derived Cardiomyocytes Recapitulate Electrical Remodeling Reminiscent of Atrial Fibrillation
Introduction: Rapid atrial stimulation is known to promote atrial fibrillation (AF) via a process of electrical remodeling that involves changes in ionic currents and ion channel gene expression. Here, we test the hypothesis that rapid stimulation of human induced-pluripotent stem cell-derived cardiomyocytes (iPS-CM) induces electrical remodeling similar to human AF.
Methods: Human iPS cells generated from peripheral blood mononuclear cells by a lentivirus-based expression system were differentiated into iPS-CM using the Sandwich Protocol. Electrical stimulation was performed at 1 Hz and 4 Hz for 8 hours. Calcium remodeling was evaluated by changes in Cav1.2 expression level using qPCR and epifluorescence measurements (fluo-4) of calcium transients (CaTs).
Results: Efficiency of iPS-CM differentiation was consistently greater than 80%. Whereas Cav1.2 mRNA levels were similar between the unpaced (control) and 1 Hz cells, cells tachypaced at 4 Hz showed significantly lower Cav1.2 levels compared with controls. Likewise, CaT magnitude was similar between control and 1 Hz, but 4 Hz pacing caused a marked reduction in CaT magnitude, slowed the rate of decay and elicited secondary calcium releases (N=10 each group, p<0.0001; ANOVA).
Conclusions: We conclude that human iPSC-CM undergo electrical remodeling reminiscent of human AF, including relevant changes in calcium channel properties and gene expression. These proof-of-principal experiments provide a platform to test the in vitro efficacy of therapeutic agents and the foundation to study the pathological substrate in familial AF.
- © 2013 by American Heart Association, Inc.