Fig. 2: TGF-β2 levels separated plaques from patients with T2D from plaques from patients without diabetes.
a Orthogonal partial least squares discriminant analysis (OPLS-DA) of 16 different growth factors measured in atherosclerotic plaques demonstrated a clear separation of plaques from patients with type 2 diabetes (T2D; red) and without diabetes (blue) (R2Y (cum) = 0.19, Q2 (cum) = 0.14; CV-ANOVA p-value = 1.1 × 10−6; n = 218 patient samples). b TGF-β1, -β2 and -β3 were identified as the three top proteins separating T2D plaques from plaques from patients without diabetes based on their variable influence on projection (VIP) scores from OPLS-DA (n = 218 patient samples). Data presented as a bar graph of VIP scores and 95% confidence intervals. Growth factors with VIP scores greater than 1 are highlighted in red. c Total protein levels of TGF-β1, -β2 and -β3 were reduced in T2D plaque tissue homogenates (n = 72 patient samples) compared to plaque tissue homogenates from patients without diabetes (n = 147 patient samples). Data presented as violin plots with lines representing median and interquartile range (IQR; 25th to the 75th percentile). Two-sided Mann–Whitney U-tests were used. d Plaque cells from donors with T2D released significantly lower levels of TGF-β isoforms compared to cells from patients without diabetes (n = 4 biological replicates). Live plaque cells were isolated from human carotid plaques and maintained in vitro for 17 h before TGF-β protein levels were assessed in cell culture supernatant. All values were normalized against total proteins. Data is presented as violin plots where lines represent median and interquartile range (IQR; 25th to the 75th percentile). Two-sided Mann–Whitney U-tests were used. TGF-β transforming growth factor-β, HGF hepatocyte growth factor, Beta-NGF beta-nerve growth factor, PIGF placental growth factor, VEGF vascular endothelial growth factor, PDGF platelet-derived growth factor, SCF stem cell factor, HB-EGF, heparin-binding EGF like growth factor, GDF growth differentiation factor, CSF-1 colony-stimulating factor-1, FGF fibroblast growth factor, EGF epidermal growth factor, GH growth hormone. Source data are provided in a source data file.
