PPARα inhibits vascular smooth muscle cell proliferation underlying intimal hyperplasia
by inducing the tumor suppressor p16INK4a
J. Clin. Invest. Florence Gizard, et al. 115:3228 doi:10.1172/JCI22756 [
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Figure 1PPARα inhibits SMC G
1/S progression. (
A and
B) G
1-arrested hSMCs (
A) and PPARα
–/– or PPARα
+/+ Sv/129 mSMCs (
B) resumed growth at T0 in normal GM. The indicated concentrations of GW7647, Wy14,643 (10 μM), or vehicle (Me
2SO) were added in the normal GM. Cells were harvested at the indicated times for measure of DNA content (expressed as arbitrary units). Values are the mean ± SEM of triplicate points from a single experiment (
n = 3/time point), which was repeated with 3 different cell preparations of primary SMCs with similar results. *
P ≤ 0.05; ***
P ≤ 0.001 vs. vehicle-treated hSMCs (
A). Values in
B followed by different symbols are statistically significantly different from each other. (
C) Western blot analysis of in-cell pRB phosphorylation was performed using an anti-pRB antibody recognizing all species of the Rb gene product on protein extracts (30 μg) from Ad-GFP or Ad-PPARα–infected hSMCs and treated with vehicle or GW7647 (600 nM) for 10 hours.