Molecular Correlates of Early Onset of Diabetic Cardiomyopathy: Possible Therapeutic Targets

Figure 8

Functional phenotyping of high glucose-treated human iPSC-derived cardiomyocytes. (a) Fluorescence ratio profile showing the intracellular free calcium transients ([Ca²⁺]_i) response to 1 Hz field stimulation using Fura-2AM in hiPSC-CMs (left). Measurement of baseline (middle) and peak (right) [Ca²⁺]_i in hiPSC-CMs with 5.5 mmol/L (control), 11 or 25 mmol/L glucose treatment. (b) [Ca²⁺]_i changes in hiPSC-CMs by inhibition of the sarcoplasmic reticulum Ca²⁺ pump with thapsigargin among the group. Peak and plateau were expressed as % of ratio changes. (c) Measurement of [Ca²⁺]_i with Fura-2AM (top, black line) and mitochondrial Ca²⁺ ([Ca²⁺]_m) using Rhod-2/AM (bottom, red line) after mitochondrial Ca²⁺ store depletion with FCCP in hiPSC-CMs. (d) The peak evoked [Ca²⁺]_i after FCCP treatment among the groups. (e) The reduction of [Ca²⁺]_m changes after FCCP treatment among the groups of hiPSC-CMs. (f) Analysis of mitochondrial membrane potential (MMP) changes using the cationic JC-1 dye as a fluorescent probe in hiPSC-CMs. The changes were expressed as the ratio of red/green fluorescence intensity (results are analyzed from 6-8 images per group; scale bar, 10 μm). Data are expressed as . , . .

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