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Peroxisome Proliferator-Activated Receptor γ Ligands Retard Cultured Vascular Smooth Muscle Cells Calcification Induced by High Glucose

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Abstract

Peroxisome proliferator-activated receptor γ (PPARγ) and its ligands have profound effects on glucose homeostasis, cardiovascular diseases, and bone metabolism. To explore the pathophysiological roles of PPARγ in diabetes with concomitant vascular calcification, we investigated changes in PPARγ expression and the effect of the PPARγ ligands troglitazone and rosiglitazone on vascular smooth muscle cell (VSMC) calcification induced by high glucose (HG, 25 mmol/L). Compared with low glucose, HG-induced VSMC calcification, and PPARγ mRNA, protein level was decreased. Troglitazone and rosiglitazone treatment markedly attenuated the VSMC calcification, whereas PPARγ antagonist GW9662 abolished the effect of rosiglitazone on calcification. Pretreatment of VSMCs with rosiglitazone, but not troglitazone, restored the loss of lineage marker expression: the protein levels of α-actin and SM-22α were increased 52 % (P < 0.05) and 53.1 % (P < 0.01), respectively, as compared with HG alone. Troglitazone and rosiglitazone reversed the change in bone-related protein expression induced by HG: decreased the mRNA levels of osteocalcin, bone morphogenetic protein 2 (BMP2), and core binding factor α 1 (Cbfα-1) by 26.9 % (P > 0.05), 50.0 % (P < 0.01), and 24.4 % (P < 0.05), and 48.4 % (P < 0.05), 41.4 % (P < 0.01) and 56.2 % (P < 0.05), respectively, and increased that of matrix Gla protein (MGP) 84.2 % (P < 0.01) and 70.0 %, respectively (P < 0.05), as compared with HG alone. GW9662 abolished the effect of rosiglitazone on Cbfα-1 and MGP expression. PPARγ ligands can inhibit VSMCs calcification induced by high glucose.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant Nos. 30770869, 30871013 to YF Qi).

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Authors and Affiliations

  1. The Key Laboratory of Remodeling-related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Ministry of Education, Beijing, 100029, China

    Ye-Bo Zhou, Chao-Shu Tang & Yong-Fen Qi

  2. Department of Physiology, Nanjing Medical University, Nanjing, 210029, China

    Ye-Bo Zhou

  3. School of Physical Education and Sports, Beijing Normal University, Beijing, 100875, China

    Jing Zhang

  4. Department of Endocrinology, The General Hospital of Civil Aviation Administration of China, Beijing, 100123, China

    Ding-Qiong Peng

  5. Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Peking University Health Science Center, Beijing, 100191, China

    Jin-Rui Chang, Yan Cai, Yan-Rong Yu, Mo-Zhi Jia, Wei Wu, You-Fei Guan, Chao-Shu Tang & Yong-Fen Qi

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Correspondence to Ding-Qiong Peng or Yong-Fen Qi.

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Ye-Bo Zhou and Jing Zhang contributed equally to this work

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Zhou, YB., Zhang, J., Peng, DQ. et al. Peroxisome Proliferator-Activated Receptor γ Ligands Retard Cultured Vascular Smooth Muscle Cells Calcification Induced by High Glucose. Cell Biochem Biophys 66, 421–429 (2013). https://doi.org/10.1007/s12013-012-9490-7

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