Fig 2: Effects of long-term noise exposure on aortic immunohistochemistry for endothelin-1, NOX2 and 3-NT. (A) Representative immunohistochemical stainings of aortic paraffin sections (20x magnification). (B) Densitometric quantification of immunohistochemical staining for ET-1, NOX2 and 3-NT in aortic tissue. Data points represent individual animals, n = 5–8. Statistical analysis with one-way ANOVA with Tukey’s multiple comparison test revealed no significant differences.

Fig 3: Cardiac hypertrophic phenotypes are recapitulated in chambered cardiac organoids treated with CH inducer EDN1. A Schematic diagram for cardiac hypertrophy modelling. B Outer (top) or inner (bottom) area against time plot of representative videos from a single CCO of each treatment condition. C–E Quantification of changes to chamber wall thickness normalized to Week 0 (C), contraction frequency (D), contraction standard deviation (E) across the time points. Each chart represents one treatment condition (Left: Control; Middle: 50 ng/ml EDN1; Right: 100 ng/ml EDN1). Each red dot represents one organoid sample analysed (n = 4–6 organoids per condition; mean ± s.e.m; Mann–Whitney U test). F Blind analysis of fractional shortening (%) in CCOs on the third week of treatment (Control n = 18, 50 ng/ml EDN1 n = 15, 100 ng/ml EDN1 n = 17; mean ± s.e.m; Welch’s t test). G Representative confocal immunofluorescence for z-line analysis of each condition at the end of Week 3. Scale bars, 20 µm. H Zline skewness (left) and Zline fraction (right) parameters are significantly affected in treated CCOs (n = 55 sections per group; mean ± s.e.m, Welch’s t test). In (C–H), significance is presented as ***P < 0.001; **P < 0.01; *P < 0.05

Fig 4: Altered calcium transients are recapitulated in chambered cardiac organoids treated with CH inducer EDN1. A Illustration depicting how the various calcium transient parameters were derived per single cardiomyocyte contraction rhythm. B Representative calcium transient profile in control, 50 ng/ml and 100 ng/ml EDN1-treated H7-GCaMP6s-derived CCOs. C–E Dot plot showing mean beat-to-beat duration (s), mean calcium transient duration (CTD) (s), mean depolarization duration (s), and repolarization duration (30th, 60th, 90th per cent) across cells analysed for 1 week (C) 2 weeks (D) and 3 weeks (E) post-EDN1 treatment. Calcium transients per organoid was measured across 30 s. Each red dot represents one organoid sample analysed. n = 10 CCOs per group; mean ± s.e.m. Data information: Statistical analysis was performed using Students two-tailed T test. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001