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Cardiovascular Diabetology
Published in: Cardiovascular Diabetology 1/2009

Open Access 01-12-2009 | Original investigation

Pioglitazone enhances collateral blood flow in ischemic hindlimb of diabetic mice through an Akt-dependent VEGF-mediated mechanism, regardless of PPARγ stimulation

Authors: Federico Biscetti, Giuseppe Straface, Vincenzo Arena, Egidio Stigliano, Giovanni Pecorini, Paola Rizzo, Giulia De Angelis, Luigi Iuliano, Giovanni Ghirlanda, Andrea Flex

Published in: Cardiovascular Diabetology | Issue 1/2009

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Abstract

Background

Type 2 diabetes mellitus (T2DM) is commonly associated with both microvascular and macrovascular complications and a strong correlation exists between glycaemic control and the incidence and progression of vascular complications. Pioglitazone, a Peroxisome proliferator-activated receptor-γ (PPARγ) ligand indicated for therapy of type T2DM, induces vascular effects that seem to occur independently of glucose lowering.

Methods

By using a hindlimb ischemia murine model, in this study we have found that pioglitazone restores the blood flow recovery and capillary density in ischemic muscle of diabetic mice and that this process is associated with increased expression of Vascular Endothelial Growth Factor (VEGF). Importantly, these beneficial effects are abrogated when endogenous Akt is inhibited; furthermore, the direct activation of PPARγ, with its selective agonist GW1929, does not restore blood flow recovery and capillary density. Finally, an important collateral vessel growth is obtained with combined treatment with pioglitazone and selective PPARγ inhibitor GW9662.

Conclusion

These data demonstrate that Akt-VEGF pathway is essential for ischemia-induced angiogenic effect of pioglitazone and that pioglitazone exerts this effect via a PPARγ independent manner.
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Metadata
Title
Pioglitazone enhances collateral blood flow in ischemic hindlimb of diabetic mice through an Akt-dependent VEGF-mediated mechanism, regardless of PPARγ stimulation
Authors
Federico Biscetti
Giuseppe Straface
Vincenzo Arena
Egidio Stigliano
Giovanni Pecorini
Paola Rizzo
Giulia De Angelis
Luigi Iuliano
Giovanni Ghirlanda
Andrea Flex
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Cardiovascular Diabetology / Issue 1/2009
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/1475-2840-8-49

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Keynote webinar | Spotlight on medication adherence

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WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

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