Figure 4.

Altered contractile dynamics and inflammatory response of cardiac MTs regulated by EC-CM communication in VMToC but not in MToC

(A–H) Quantification of the contraction parameters presented as percentage change from the baseline mean of spontaneous beating condition, after 1 h (A–D) and 6 h (E–H) incubation with vehicle or L-NAME (1 mM): contraction duration (A and E); time to peak (B and F); relaxation time (C and G); peak-to-peak time (D and H) in MTs with LUMC0059iCTRL03 hiPSC-CMs. Error bars are shown as mean ± SD from MToC N = 3, n > 28 (vehicle) and n > 27 (L-NAME); VMToC N = 3, n > 24 (vehicle) and n > 27 (L-NAME); three independent experiments with at least seven MTs in each experiment.

(I–K) Quantification of pro-inflammatory cytokines from the medium after 12 h incubation of IL-1β (10 ng/mL): IL-6 (I); IL-8 (J); MCP1/CCL2 (K) in MTs with LUMC0059iCTRL03 hiPSC-CMs. Y axis shows concentration (pg/mL). Error bars are shown as mean ± SD. MToC N = 3, n > 3; VMToC N = 3, n > 3; three independent experiments; medium was collected from at least with three different microfluidic channels in each experiment.

(L–O) Quantification of the contraction parameters presented as percentage change from the baseline mean of spontaneous beating condition after 12 h incubation with vehicle or IL-1β (10 ng/mL): contraction duration (L); time to peak (M); relaxation time (N); peak-to-peak time (O) in MTs with LUMC0059iCTRL03 hiPSC-CMs. Error bars are shown as mean ± SD from MToC N = 3, n = 26 (vehicle) and n = 30 (IL-1β); VMToC N = 3, n = 25 (vehicle) and n = 31 (IL-1β); three independent experiments with at least seven MTs in each experiment. Kruskal-Wallis test with Dunn’s multiple comparisons test (A–H, L–O), two-way ANOVA with Šidák’s multiple comparisons test (I–K), ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001; ∗∗∗∗p < 0.0001; ns, not significant.

See also Figure S4.