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. Author manuscript; available in PMC: 2022 Jun 25.
Published in final edited form as: Circ Res. 2021 Apr 15;129(1):33–46. doi: 10.1161/CIRCRESAHA.121.319060

Figure 4. An immuno-cardiac co-culture platform based high content screen identifies FDA-approved drug candidates that protect CMs from macrophage-mediated cell apoptosis.

Figure 4.

A, Scheme of the high content screen and primary screening results.

B, Chemical structure and inhibitory curve of ranolazine.

C, Chemical structure and inhibitory curve of tofacitinib.

D, Immunostaining and quantification of relative mean ROS intensity in MYH6:mCherry+ CMs under 10 μM ranolazine or 0.5 μM tofacitinib treated virus-immuno-cardiac co-culture platform containing H9-derived CMs and H9-derived macrophages infected with SARS-CoV-2 virus (MOI=0.1). Scale bar= 50 μm.

E, Confocal imaging and quantification of relative mean CASP3 intensity in cTNT+ CMs under 10 μM ranolazine or 0.5 μM tofacitinib treated virus-immuno-cardiac co-culture platform containing H9-derived CMs and H9-derived macrophages infected with SARS-CoV-2 virus (MOI=0.1). Scale bar= 50 μm.

F, Immunostaining and quantification of relative mean ROS intensity in adult CMs under 10 μM ranolazine or 0.5 μM tofacitinib treated virus-immuno-cardiac co-culture platform containing adult human CMs and H9-derived macrophages infected with SARS-CoV-2 virus (MOI=0.1). Scale bar= 50 μm.

G, Confocal imaging and quantification of relative mean CASP3 intensity in adult CMs under 10 μM ranolazine or 0.5 μM tofacitinib treated virus-immuno-cardiac co-culture platform containing adult human CMs and H9-derived macrophages infected with SARS-CoV-2 virus (MOI=0.1). Scale bar= 50 μm.

H, Confocal imaging and quantification of relative mean CASP3 intensity in cTNT+ CMs under 10 μM ranolazine or 0.5 μM tofacitinib treated virus-immuno-cardiac co-culture platform containing H9-derived CMs and H9-derived macrophages infected with SARS-CoV-2 virus for long term co-culture (7 days co-culture, MOI=0.1). Scale bar= 50 μm.

I, Confocal imaging and quantification of relative mean CASP3 intensity in adult CMs under 10 μM ranolazine or 0.5 μM tofacitinib treated virus-immuno-cardiac co-culture platform containing adult human CMs and H9-derived macrophages infected with SARS-CoV-2 virus for long term co-culture (7 days co-culture, MOI=0.1). Scale bar= 50 μm.

N=3 independent biological replicates. Data was presented as mean ± STDEV. P values were calculated by one-way ANOVA. *P < 0.05, **P < 0.01, and ***P < 0.001.