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. 2023 Jul 21;14:4416. doi: 10.1038/s41467-023-39934-z

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© The Author(s) 2023

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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 2 — a Venn diagram showing the numbers of genes involved in ECM remodeling that are differentially expressed in PA samples of LHD w/o PH patients vs. PH-LHD patients. A principal component analysis (PCA) plot depicts sample clustering based on ECM gene expression profiles. Heat maps display log2-fold changes in the expression of fibrillar and fibril-associated collagens and genes involved in elastic fiber assembly/disassembly in PA samples of LHD w/o PH and PH-LHD patients relative to donor samples. b Box-and-whisker plot showing the collagen-to-elastin ratio in biologically independent PA samples from donors (n = 9), LHD w/o PH (n = 9), or PH-LHD (n = 11) patients (p = 0.01 for LHD w/o PH vs. donor, and p = 0.0002 for PH-LHD vs. donor). c Representative images of EVG-stained PA medial walls from a donor, an LHD w/o PH patient, and a PH-LHD patient (left panels). The center panels show collagen-positive area only, right panels show elastic fibers only. Notably, the combination of hematoxylin with EVG also stains cell nuclei, which are hence included in the elastin stain signal on the right panel. The presented images are derived from biologically independent PA samples from donors (n = 9), LHD w/o PH (n = 9), and PH-LHD (n = 11) patients. d Immunoblots show protein levels of MMP2 (70 kDa), MMP12 (52 kDa), and GAPDH (loading control, 37 kDa) in biologically independent PA samples from donors (n = 5), LHD w/o PH (n = 7), and PH-LHD (n = 7) patients and MMP9 (82 kDa), MMP13 (53 kDa), and GAPDH (loading control, 37 kDa) in biologically independent PA samples from donors (n = 6), LHD w/o PH (n = 6), and PH-LHD (n = 6) patients. Box-and-whisker plots show quantitative densitometric data of MMP expression normalized to GAPDH and the mean of the donor controls. MMP expression differs between groups as follows: MMP12 (p = 0.048 for PH-LHD vs. donor), MMP9 (p = 0.093 for LHD w/o PH vs. donor and p = 0.0087 for PH-LHD vs. donor), MMP13 (p = 0.0152 for LHD w/o PH vs. donor and p = 0.0022 for PH-LHD vs. donor). Box-and-whisker plots overlaid with dot plots (b, d) show individual data points, mean (rectangle), median (line within the box), lower and upper 25% quartiles (limits of the box), 1.5 IQR (whiskers), and outliers (if applicable). Statistics: b Unpaired two-tailed Kruskal-Wallis one-way ANOVA on ranks followed by pairwise multiple comparisons (Dunn’s test). d Unpaired two-tailed Mann–Whitney U test (vs. donor). Source data are provided as a Source Data file. Full scan blots are provided in Suppl. Fig. 12.