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. 2022 Sep 15;13:5409. doi: 10.1038/s41467-022-33152-9

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a Global gene expression heatmap for differentially expressed genes in the left ventricle (LV), ventricular septum, and right ventricle (RV) (n = 3–4). b, c Ingenuity pathway analysis of differentially expressed genes. Significance of the association between the dataset and the canonical pathway (−log (p-value) and fold change), and the z-score prediction are shown. The significance values are calculated by the right-tailed Fisher’s exact test. d–f mRNA expression of CFD, C3, and C3AR1 in human RV and LV (n = 3, p = 0.0004, p < 0.0001, p = 0.001). Data are presented as mean ± standard error of the mean (SEM). g–i mRNA expression of Cfd, C3, and C3ar1 in sham-operated (n = 4–5, p = 0.0006, p < 0.0001, p = 0.003) and PAC model mice (n = 4–5, p = 0.024, p = 0.1798, p = 0.0207). Data are presented as mean ± SEM. j, k Measured values of the echocardiogram in sham and PAC models of wild type (WT) and C3 knockout (C3KO) mice (n = 3–5, j p = 0.001, p < 0.0001. k p < 0.0001, p = 0.002). The RV contractile function (right ventricular fractional shortening [RV FS]) and RV size (right ventricular end-diastolic diameter [RVDd]) were evaluated. Data are presented as mean ± standard deviation (SD). l Representative immunostaining images for C3d in the RV of PAC model and sham-operated mice (n = 3). m Measured values of the catheter analysis in sham and PAC models of WT and C3KO mice (n = 3, p = 0.0174, p = 0.0059). RV end-diastolic pressure was evaluated. n, o Representative Azan staining images of the heart in WT and C3KO mice with PAC (n = 3). p–s mRNA expression of Nppb, Myh7, Col3a1, and Ccn2 in the LV, ventricular septum, and RV of WT and C3KO mice with PAC (n = 3–4, p = 0.00194, p = 0.0010, p = 0.0029, p = 0.0017). Data are presented as mean ± SEM. mRNA expression of target genes was normalised to that of Gapdh. Significance was assessed using a two-tailed unpaired Student’s t-test. *p < 0.05; **p < 0.01.