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01-11-2012 | Original Contribution

Pioglitazone attenuates progression of aortic valve calcification via down-regulating receptor for advanced glycation end products

Authors: Fei Li, Zhejun Cai, Fang Chen, Xucong Shi, Qiao Zhang, Si Chen, Jiawei Shi, Dao Wen Wang, Nianguo Dong

Published in: Basic Research in Cardiology | Issue 6/2012

Abstract

Receptor for advanced glycation end products (RAGE) is associated with inflammation and the progression of cardiovascular diseases. The current study tested the hypothesis that RAGE is involved in the pathogenesis of aortic valve (AV) calcification. Pioglitazone attenuated AV calcification in experimental hypercholesterolemic rabbits via down-regulation of RAGE. Male New Zealand rabbits weighing 2.5–3.0 kg were randomly divided into three groups: control group, high cholesterol + vitamin D₂ (HC + vitD₂) group and HC + vitD₂ supplemented with pioglitazone group. Compared with HC + vitD₂ group, pioglitazone significantly inhibited the progression of AV calcification assessed by echocardiography. HC + vitD₂ diet markedly increased RAGE expression, oxidative stress, inflammatory cells infiltration and osteopontin expression. These changes were also significantly attenuated by administration of pioglitazone. Cultured porcine aortic valve interstitial cells (VICs) were used as in vitro model. We found that advanced glycation end products of bovine serum albumin markedly increased the expression of RAGE, induced high levels of production of pro-inflammatory cytokines and promoted osteoblastic differentiation of VICs. However, these effects were found to be remarkably suppressed by siRNA silencing of RAGE and pioglitazone as well. Our data provide evidence that RAGE activation-induced inflammation promotes AV calcification in hypercholesterolemic rabbits, which can be attenuated by pioglitazone treatment. This beneficial effect is associated with remarkable down-regulation of RAGE expression.

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Title: Pioglitazone attenuates progression of aortic valve calcification via down-regulating receptor for advanced glycation end products
Authors: Fei Li
Zhejun Cai
Fang Chen
Xucong Shi
Qiao Zhang
Si Chen
Jiawei Shi
Dao Wen Wang
Nianguo Dong
Publication date: 01-11-2012
Publisher: Springer-Verlag
Published in: Basic Research in Cardiology / Issue 6/2012
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-012-0306-0

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Pioglitazone attenuates progression of aortic valve calcification via down-regulating receptor for advanced glycation end products

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