Human induced pluripotent stem cell-derived cardiomyocytes to study inflammation-induced aberrant calcium transient

  1. Yuki Tatekoshi
  2. Chunlei Chen
  3. Jason Solomon Shapiro
  4. Hsiang-Chun Chang
  5. Malorie Blancard
  6. Davi M Lyra-Leite
  7. Paul W Burridge
  8. Matthew Feinstein
  9. Richard D'Aquila
  10. Priscilla Hsue
  11. Hossein Ardehali  Is a corresponding author
  1. Feinberg Cardiovascular and Renal Research Institute, Northwestern University, United States
  2. Department of Pharmacology, Northwestern University, United States
  3. Department of Medicine, Northwestern University, United States
  4. Department of Medicine, University of California, San Francisco, United States
6 figures, 1 table and 1 additional file

Figures

Figure 1 with 2 supplements
Analyses of calcium transient in hiPSC-CMs treated with cytokines and/or MitoTempo.

Normalized downstroke time (A), decay time (B), and beating rate as assessed by beats per minute (C) in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) treated with bovine …

Figure 1—source data 1

Analyses of calcium transient in hiPSC-CMs treated with cytokines and/or MitoTempo.

https://cdn.elifesciences.org/articles/95867/elife-95867-fig1-data1-v1.xlsx
Figure 1—figure supplement 1
A representative calcium transient curve in hiPSC-CMs and their mitochondrial potential.

(A) Representative image of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM). Scale bar represents 100 μm. (B) Representative curves of calcium transient and its derivative in …

Figure 1—figure supplement 1—source data 1

A epresentative image of hiPSC-CMs, a calcium transient curve, and a relative dF/dt curve.

https://cdn.elifesciences.org/articles/95867/elife-95867-fig1-figsupp1-data1-v1.xlsx
Figure 1—figure supplement 1—source data 2

Relative TMRE fluorescence in hiPSC-CMs with cytokine treatments.

https://cdn.elifesciences.org/articles/95867/elife-95867-fig1-figsupp1-data2-v1.xlsx
Figure 1—video 1
Representative video of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) contracting spontaneously in a culture dish.

Scale bar represents 100 μm.

Oxygen consumption rate (OCR) in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) treated with cytokines and antioxidant agent N-acetylcysteine (NAC).

(A) OCR trace of hiPSC-CM treated with bovine serum albumin (BSA), TNF-α, IFN-γ, TNF-α + IFN-γ, TNF-α + NAC, IFN-γ + NAC, and TNF-α + IFN-γ + NAC. (B–D) Bar graph summary of data in (A) with OCR at …

Figure 2—source data 1

OCR curve in hiPSCs treated with cytokines and NAC.

https://cdn.elifesciences.org/articles/95867/elife-95867-fig2-data1-v1.xlsx
Figure 2—source data 2

OCR at baseline, after CCCP treatment and after rotenone and antimycin A treatment.

https://cdn.elifesciences.org/articles/95867/elife-95867-fig2-data2-v1.xlsx
Figure 3 with 1 supplement
Decay time in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) after treatment with TNF-α and various antiretroviral therapy (ART) drugs.

(A) Decay time after treatment with TNF-α, tenofovir, and TNF-α+tenofovir. (B) Decay time after treatment with TNF-α, darunavir, and TNF-α+darunavir. (C) Decay time after treatment with TNF-α, …

Figure 3—source data 1

Normalized decay times in hiPSC-CMs treated with TNF-α and/or anti-HIV drugs.

https://cdn.elifesciences.org/articles/95867/elife-95867-fig3-data1-v1.xlsx
Figure 3—figure supplement 1
Cell viability and ROS levels in hiPSC-CMs treated with anti-HIV drugs.

Cell viability (A) and cellular reactive oxygen species (ROS) levels (B) in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) exposed to concentrations ranging from between 3 nM …

Figure 3—figure supplement 1—source data 1

Cell viability and ROS levels in hiPSC-CMs treated with anti-HIV drugs.

https://cdn.elifesciences.org/articles/95867/elife-95867-fig3-figsupp1-data1-v1.xlsx
Figure 4 with 1 supplement
Decay time in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) after treatment with TNF-α and riociguat, sildenafil citrate, PF-04447943, and dapagliflozin.

(A) Decay time after treatment with TNF-α, sGS agonist riociguat, and TNF-α + riociguat (N = 8–21). (B) Decay time after treatment with TNF-α, sildenafil citrate, and TNF-α + sildenafil citrate (N = …

Figure 4—source data 1

Normalizaed decay times in hiPSC-CMs treated with TNFα and Riociguat, Sildenafil citrate and PF-04447943.

https://cdn.elifesciences.org/articles/95867/elife-95867-fig4-data1-v1.xlsx
Figure 4—source data 2

Analyses of calcium transient in hiPSC-CMs treated with TNFα, INFγ and 10 μM Dapagliflozin.

https://cdn.elifesciences.org/articles/95867/elife-95867-fig4-data2-v1.xlsx
Figure 4—figure supplement 1
Analyses of calcium transient in hiPSC-CMs treated with TNFa and/or 1 μM Dapagliflozin.

Decay time (A) and downstroke time (B) in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) after treatment with TNF-α and 1 μM of dapagliflozin.

N = 5–21, Data were analyzed by ordinary one-way ANOVA and post hoc Tukey’s multiple-comparison test. Bars represent group mean, and error bars indicate standard error of the mean.

Figure 5 with 2 supplements
Ca2+-decay time of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and angiogenic function of ECs after treatment with serum from group 1 HIV+ patients with diastolic dysfunction (DD).

(A–C) Pooled normalized decay time (A), downstroke time (B), and beating rate (C) in hiPSC treated with 10% serum for 48 hr from group 1 HIV+ patients with DD (3 values from cells treated with each …

Figure 5—source data 1

Analyses of calcium transient in hiPSCs treated with serum from HIV patients.

https://cdn.elifesciences.org/articles/95867/elife-95867-fig5-data1-v1.xlsx
Figure 5—source data 2

Quantitative analyses of tube formation assay in HUVECs treated with serum from HIV patients.

https://cdn.elifesciences.org/articles/95867/elife-95867-fig5-data2-v1.xlsx
Figure 5—figure supplement 1
Representative images of formed tube structure with human umbilical vein endothelial cells (HUVEC) treated with 2% serum from HIV+ patients with high or low myocardial perfusion reserve (MPR) for 20 hr.

Scale bars represent 500 μm.

Figure 5—figure supplement 2
Representative magnified images of formed tube structure with human umbilical vein endothelial cells (HUVEC) treated with 2% serum from HIV+ patients with high or low myocardial perfusion reserve (MPR) for 20 hr.

Scale bars indicate 250 μm.

Diastolic function of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) and angiogenic function of ECs after treatment with serum from HIV+ patients with diastolic dysfunction (DD) (group 2).

(A, B) Individual normalized decay time 3 hr (N = 3–9) (A) or 24 hr (N = 3–13) (B) after treatment of hiPSC-CM with 2% serum from patients. (C, D) Pooled decay time data from patients in (A) and (B) …

Figure 6—source data 1

Normalized decay time in iPS-CMs treated with HIV patient serum with or without diastolic dysfunction.

https://cdn.elifesciences.org/articles/95867/elife-95867-fig6-data1-v1.xlsx
Figure 6—source data 2

Quantitative analyses of tube formation assay in HUVECs treated with serum from HIV patients.

https://cdn.elifesciences.org/articles/95867/elife-95867-fig6-data2-v1.xlsx

Tables

Table 1
Clinical characteristics of study population for group 1.
ParticipantAgeHigh or low myocardial perfusion reserve groupSexCD4 countDiabetes mellitus?Active cigarette smoking?Hypertension?Coronary artery disease diagnosis?Left ventricular ejection fractionMyocardial perfusion reserve
150HighMale487NoYesYesNo642.74
262LowMale703NoNoYesYes591.03
364HighMale321NoNoNoYes653.43
455HighMale749NoNoYesYes591.90
571LowMale1743NoNoYesYes551.03
659LowMale678NoNoYesNo521.13

Additional files

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