Kristopher G. Maier, PhD, Xuan Han, Benjamin Sadowitz, MD, Karen L

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Thrombospondin-1: A proatherosclerotic protein augmented by hyperglycemia Kristopher G. Maier, PhD, Xuan Han, Benjamin Sadowitz, MD, Karen L. Gentile, MPS, Frank A. Middleton, PhD, Vivian Gahtan, MD Journal of Vascular Surgery Volume 51, Issue 5, Pages 1238-1247 (May 2010) DOI: 10.1016/j.jvs.2009.11.073 Copyright © 2010 Terms and Conditions

Fig 1 Volcano plot shows microarray data obtained from 25 mM glucose vs 5 mM glucose. Thirty genes were altered by 25 mM glucose (3 experiments). The x-axis of these plots represents the fold change in gene expression in a log2 format, thus any point <0 represents a down-regulated gene. The y-axis is the –log10 of the P value and all points in black are significant (P < .05). Journal of Vascular Surgery 2010 51, 1238-1247DOI: (10.1016/j.jvs.2009.11.073) Copyright © 2010 Terms and Conditions

Fig 2 Volcano plot shows microarray data obtained from thrombospondin-1 (TSP-1) vs 5 mM glucose-treated vascular smooth muscle cells. TSP-1 (3 experiments) altered 212 genes. The x-axis of these plots represents the fold change in gene expression in a log2 format; thus, any point <0 represents a down-regulated gene. The y-axis is the –log10 of the P value and all points in black are significant (P < .05). The three most up-regulated genes were UGDH, TGFβ2, and HAS2. Journal of Vascular Surgery 2010 51, 1238-1247DOI: (10.1016/j.jvs.2009.11.073) Copyright © 2010 Terms and Conditions

Fig 3 Volcano plot shows microarray data obtained from 25 mM glucose + thrombospondin-1 (TSP-1) vs 5 mM glucose-treated vascular smooth muscle cells. TSP-1 (3 experiments) altered 2822 genes. The x-axis of these plots represents the fold change in gene expression in a log2 format; thus, any point <0 represents a down-regulated gene. The y-axis is the –log10 of the P value, and all points in black are significant (P < .05). Journal of Vascular Surgery 2010 51, 1238-1247DOI: (10.1016/j.jvs.2009.11.073) Copyright © 2010 Terms and Conditions

Fig 4 Canonical pathways affected by thrombospondin-1 (TSP-1) treatment compared with 5 mM glucose treatment of vascular smooth muscle cells as determined by Ingenuity pathway analysis. Data were analyzed with a cutoff of 30%, and only pathways that crossed a significance threshold of P < .05 are displayed. TSP-1 treatment altered 13 canonical pathways. IGF-1, Insulin-like growth factor-1; RAR, retinoic acid receptor; TGF-β, transforming growth factor β. Journal of Vascular Surgery 2010 51, 1238-1247DOI: (10.1016/j.jvs.2009.11.073) Copyright © 2010 Terms and Conditions

Fig 5 Canonical pathways affected by 25 mM glucose + thrombospondin-1 (TSP-1) treatment compared with 5 mM glucose treatment of vascular smooth muscle cells as determined by Ingenuity pathway analysis. Data were analyzed with a cutoff of 30%, and only pathways that crossed a significance threshold of P < .05 are displayed. Treatment with 25 mM glucose + TSP-1 altered 53 canonical pathways. EGF, Endothelial growth factor; ERK, extracellular signal-regulated kinase; IGF-1, insulin-like growth factor 1; IL-10, interleukin-10; IL-6, interleukin 6; MAPK, mitogen-activated protein kinase; PDGF, platelet-derived growth factor; PPAR, peroxisome proliferator-activated receptor; RAR, retinoic acid receptor; TGF-, transforming growth factorβ; VDR/RXR, vitamin D3 receptor/retinoid-X receptor; BMP, bone morphogenetic protein; SAPK/JNK, stress-activated protein kinase/c-Jun NH2-terminal kinase; TRK, neurotrophin receptor; TR, thyroid hormone receptor; AKT, protein kinase b; PI3K, phosphatidylinositol 3 kinase; LXR, liver X receptor; IL-8, interleukin 8; FGF, fibroblast growth factor; IL-10, interleukin 10; PTEN, phosphatase and tensin homolog. Journal of Vascular Surgery 2010 51, 1238-1247DOI: (10.1016/j.jvs.2009.11.073) Copyright © 2010 Terms and Conditions