Fig. 6: Quantitative proteomics shows that increased protein nitration is a signature of MFS in mice and humans.

Quantitative proteomics analysis of plasma samples from a untreated WT mice (n = 7), MFS mice (n = 7), and DetaNO-treated WT mice (n = 6) and b MFS patients (n = 23) and healthy donors (n = 30). Data were analyzed using the SanXoT package. Theoretical, normal distribution; Nitro-proteins, cumulative distributions of indicated nitrated protein values corrected to the values for nonmodified peptides from the same protein; All-proteins, cumulative distributions of nonmodified peptides. Data are expressed in standardized log2-ratios (Zq) relative to a untreated WT or b healthy donors (Control). Differences were analyzed by two-tailed Kolmogorov-Smirnov test (p-values are shown; n.s., not significant). Representative annotated fragmentation spectra for 2 mouse nitro-peptides are provided in Supplementary Fig. 9. All MS/MS spectra of identified tryptic nitro-peptides are provided in the Data availability section. c List of nitrated peptides showing significantly higher abundance in MFS patients. The heatmap shows standardized log2-ratios (Zpq) and statistical significance calculated using limma analysis. The annotated fragmentation spectra of these 7 nitro-peptides are provided in Supplementary Fig. 10. d Nitrated plasma index, defined as the weighted mean of the nitro-peptides listed in c, for 23 MFS patients and 30 healthy donors (Control). Each data point denotes an individual, boxes enclose the interquartile range (IQR), the line in the box shows the centre (median), and whiskers extend 1.5 times above and below the IQR. Differences were analyzed by unpaired two-tailed Student’s t-test. e Quantitative proteomics analysis of pooled aortic samples from 12 untreated WT mice (n = 6 pools) and 12 MFS mice (n = 6 pools). Nitrated protein distributions are shown as in a and b. Differences were analyzed by two-tailed Kolmogorov-Smirnov test. f Barplots showing standardized log2-ratios (Zq) integrated by condition (untreated WT and MFS) for significantly upregulated nitro-proteins related to the cytoskeleton: thrombospondin type-1 domain-containing protein 4 (THSD4), coronin 1-C (CORO1C), latent-transforming growth factor beta 2 and 4 (LTBP2, LTBP4), actin aortic smooth muscle (ACTA2), tensin 3 (TNS3), dynein heavy chain 10 (DNAH10), and tubulin beta 4 chain (TUBB4B). Differences were analyzed by limma statistical analysis (exact p-values are shown). Source data are provided in the Source Data file.