Pioglitazone induces vascular smooth muscle cell apoptosis through a peroxisome proliferator-activated receptor-gamma, transforming growth factor-beta1, and a Smad2-dependent mechanism.

Abstract:

:Thiazolidinediones, such as pioglitazone, seem to exert direct antiatherosclerotic and antirestenotic effects on type 2 diabetes, in part due to an induction of vascular smooth muscle cell (VSMC) apoptosis. We aimed to study the role of transforming growth factor (TGF)-beta in rat aortic VSMC. Pioglitazone at 100 micromol/l increased apoptosis without affecting DNA synthesis, and this effect was reversed by an anti-TGF-beta1 antibody. Extracellular TGF-beta1 levels were rapidly increased after treatment with pioglitazone in a peroxisome proliferator-activated receptor (PPAR)-gamma-dependent mechanism because this secretion was blocked by the PPAR-gamma inhibitor GW9662. Pioglitazone subsequently increased the nuclear recruitment of phospho-Smad2, without any effect on protein expression. According to our results, we propose that the apoptotic effect of pioglitazone on VSMC depends on the following sequence: PPAR-gamma activation, TGF-beta1 release, and selective phospho-Smad2 nuclear recruitment. Management of Smad signaling on VSMC might provide future clinical benefits in vascular diseases.

journal_name

Diabetes

journal_title

Diabetes

authors

Redondo S,Ruiz E,Santos-Gallego CG,Padilla E,Tejerina T

doi

10.2337/diabetes.54.3.811

subject

Has Abstract

pub_date

2005-03-01 00:00:00

pages

811-7

issue

3

eissn

0012-1797

issn

1939-327X

pii

54/3/811

journal_volume

54

pub_type

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