1. The cyclolignan picropodophyllin attenuates intimal hyperplasia after rat carotid balloon injury by blocking insulin-like growth factor-1 receptor signaling 
Anton Razuvaev, MD, Bimma Henderson, MD, Leonard Girnita, MD, PhD, Olle Larsson, MD, PhD, Magnus Axelson, MD, PhD, Ulf Hedin, MD, PhD, Joy Roy, MD, PhD 
Journal of Vascular Surgery 
Volume 46, Issue 1, Pages (July 2007)
DOI: /j.jvs
Copyright © 2007 The Society for Vascular Surgery Terms and Conditions

2. Fig 1
A, Effects of picropodophyllin (PPP) on neointima formation after balloon injury. Photomicrographs show cross-sections of rat carotid arteries 2 weeks after injury. Arrow points to the internal elastic lamina (IEL); arrowhead points to the external elastic lamina (EEL). B, Morphometric quantification of the effect of PPP treatment (n = 7; control, n = 6) on neointima formation presented as changes in intima-to-media ratio (left panel) and lumen area (right panel). Data are shown as mean ± SD (*P < .05; **P < .001). C, Quantification of cells positive for proliferating cellular nuclear antigen (PCNA) on day 4 after balloon injury (n = 3 in each group). Data are shown as median ± SD (P < .05).
Journal of Vascular Surgery  , DOI: ( /j.jvs )
Copyright © 2007 The Society for Vascular Surgery Terms and Conditions

3. Fig 2
Effect of picropodophyllin (PPP) on smooth muscle cell (SMC) proliferation. SMC cultures were synchronized in F-12/0.1% bovine serum albumin, stimulated with 10 ng/mL insulin-like growth factor-1 (IGF-1), or 10% fetal bovine serum (FBS), in the presence or absence of PPP. A, Cell number and B, 3[H] thymidine incorporation were determined as described in “Methods.” Controls were treated with mitogen only (white bar). Data are shown as mean ± SD (*P < .05, **P < .001).
Journal of Vascular Surgery  , DOI: ( /j.jvs )
Copyright © 2007 The Society for Vascular Surgery Terms and Conditions

4. Fig 3
Effect of picropodophyllin (PPP) on apoptosis in smooth muscle cells (SMCs) SMC cultures were synchronized in F12/0.1% bovine serum albumin, stimulated with 30 ng/mL insulin-like growth factor-1 (IGF-1) or 10% fetal bovine serum (FBS) in the presence or absence of PPP, and annexin V labelling determined by flow cytometry as described in Methods. A, Cells positive for annexin V and negative for propidium iodide (early apoptosis). B, Cells all positive for annexin V (total apoptosis). Data are shown as mean ± SD of three experiments (P >.05).
Journal of Vascular Surgery  , DOI: ( /j.jvs )
Copyright © 2007 The Society for Vascular Surgery Terms and Conditions

5. Fig 4
The effects of picropodophyllin (PPP) on phosphorylation of insulin-like growth factor-1R (IGF-1R) and protein kinase B (Akt) in (A) balloon-injured carotid arteries and (B) cultured smooth muscle cells SMCs. A, Six arteries were retrieved 2 days after injury, and proteins were isolated for Western blotting using antibodies against IGF-1R, phosphorylated IGF-1R (pIGF-1R), phosphorylated Akt (pAkt), and Akt as described in “Methods.” IGF-1R and Akt phosphorylation was only induced after injury and was blocked by PPP treatment. B, In IGF-1–stimulated SMC cultures, PPP decreased IGF-1R and Akt phosphorylation in a dose-dependent manner with no effect on total Akt expression.
Journal of Vascular Surgery  , DOI: ( /j.jvs )
Copyright © 2007 The Society for Vascular Surgery Terms and Conditions

6. Fig 5
The effects of picropodophyllin (PPP) on phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) in cultured smooth muscle cells. A, PPP, unlike wortmannin (Wt), did not affect Akt phosphorylation in cells treated with platelet-derived growth factor (PDGF). B, ERK phosphorylation after 15 minutes was decreased by PPP in cells stimulated with IGF-1, but not with PDGF.
Journal of Vascular Surgery  , DOI: ( /j.jvs )
Copyright © 2007 The Society for Vascular Surgery Terms and Conditions