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Isolation and Characterization of Primary Rat Valve Interstitial Cells: A New Model to Study Aortic Valve Calcification
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Isolation and Characterization of Primary Rat Valve Interstitial Cells: A New Model to Study Aortic Valve Calcification

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

Fei Li1, Zhejun Cai, Fang Chen

  • 1Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Basic Research in Cardiology
|October 17, 2012
PubMed

Insights

Receptor for advanced glycation end products (RAGE) promotes aortic valve calcification through inflammation. Pioglitazone treatment down-regulates RAGE, significantly reducing calcification in hypercholesterolemic rabbits.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Pharmacology

Background:

  • Receptor for advanced glycation end products (RAGE) is implicated in inflammation and cardiovascular disease progression.
  • Aortic valve (AV) calcification is a significant contributor to cardiovascular morbidity.
  • The role of RAGE in the pathogenesis of AV calcification requires further elucidation.

Purpose of the Study:

  • To investigate the involvement of RAGE in the development of aortic valve calcification.
  • To determine the therapeutic potential of pioglitazone in mitigating AV calcification via RAGE modulation.

Main Methods:

  • Aortic valve calcification was induced in hypercholesterolemic rabbits using a high-cholesterol diet and vitamin D2.
  • Animals were treated with pioglitazone to assess its effects on AV calcification, RAGE expression, oxidative stress, and inflammation.
  • Porcine aortic valve interstitial cells (VICs) were used in vitro to study the effects of advanced glycation end products and pioglitazone on RAGE expression and osteoblastic differentiation.

Main Results:

  • Pioglitazone significantly inhibited the progression of AV calcification in rabbits compared to the control group.
  • High-cholesterol diet increased RAGE expression, oxidative stress, inflammatory cell infiltration, and osteopontin expression, which were attenuated by pioglitazone.
  • In vitro, advanced glycation end products increased RAGE expression, pro-inflammatory cytokine production, and osteoblastic differentiation in VICs, effects suppressed by RAGE silencing or pioglitazone.

Conclusions:

  • RAGE activation-induced inflammation plays a crucial role in promoting aortic valve calcification in hypercholesterolemic conditions.
  • Pioglitazone demonstrates a beneficial effect in attenuating AV calcification by down-regulating RAGE expression and associated inflammatory pathways.

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