Fig. 5: MMP2 is released from synthetic vascular smooth muscle cells and MMP2 induced TGF-β2 cleavage is reduced by hyperglycemia.

a Schematic figure illustrating the interplay between matrix metalloproteinase 2 (MMP2) and TGF-LAP complex cleavage to induce collagen production through the release of TGF-β2. b MMP2 but not MMP9 levels in plaque tissue homogenates were significantly lower in plaques from patients with type 2 diabetes (T2D; n = 70 patient samples) compared to patients without diabetes (n = 134 patient samples). Results are presented as violin plots with dotted lines indicating the median levels and the interquartile range (25th to the 75th percentile). Two-sided Mann–Whitney U-tests were used. c Heatmap showing Spearman correlation coefficients between the three TGF-β isoforms and MMP2 and MMP9 levels in plaques from patients without diabetes (n = 134 patient samples) and patients with T2D (n = 70 patient samples). The color scale represents the correlation coefficient. d Zymography showing reduced MMP2 activity in human atherosclerotic plaque cell isolates from patients with T2D compared to cells from patients without diabetes. n = 4 biological replicates in each group. Lines indicating mean (dashed) ± standard deviation (SD) of the ratio between active and pro-MMP2. Two-sided Student’s t-test was used. e t-SNE plot demonstrating that MMP2 is mainly expressed by synthetic vascular smooth muscle cells (cluster 3 cells) in the human plaque single-cell RNA sequencing. The color scale represents log-normalized counts of gene expression. f Hyperglycemic conditions reduced MMP2 activity, assessed by zymography, in synthetic human coronary arterial smooth muscle cells (HCASMC). n = 10 biological replicates from five independent experiments. One-way repeated measure ANOVA followed by Dunnett post-hoc tests (two-sided) were used. Results are presented as mean ± SD. TGF transforming growth factor, MMP matrix metalloproteinase. Source data are provided in the source data file.