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PPARγ Agonist Ameliorates the Impaired Fluidity of the Myocardial Cell Membrane and Cardiac Injury in Hypercholesterolemic Rats

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Abstract

Hypercholesterolemia can increase the risk of cardiac injury, but the underlying mechanisms are not fully understood. The present study aimed to determine whether changes in the fluidity of the cardiomyocyte membrane may contribute to the increased susceptibility to myocardial ischemia/reperfusion (MI/R) injury observed in hypercholesterolemic rats. Male Wistar rats were fed a normal (n = 24) or high-cholesterol diet (n = 32) for 10 weeks. At the 6th week, the rats in the high-cholesterol diet group were treated with vehicle (n = 16, HC + V) or pioglitazone (n = 16, HC + PIO), a peroxisome proliferator-activated receptor-γ (PPARγ) agonist, and treatment lasted for the next 4 weeks. Rats in HC + V group displayed less membrane fluidity, a greater membrane cholesterol-to-phospholipid ratio (C/P), less Na+–K+-ATPase activity, and less cAMP content in their myocardial cells than rats fed a normal diet. A strong positive correlation was observed between membrane fluidity and cardiac injury, i.e., the myocardial infarct size when subjected to MI/R (30 min/24 h). Treatment with PIO restored much of the lost hypercholesterolemia-induced myocardial cell membrane fluidity, decreased membrane C/P ratio, increased Na+–K+-ATPase activity and cardiac cell cAMP content, improved cardiac function, and reduced the sizes of myocardial infarcts. Results demonstrated that hypercholesterolemia-induced decreased myocardial cell membrane fluidity may contribute to the increased susceptibility to cardiac injury, and PPARγ agonists may have therapeutic value in patients with hypercholesterolemia.

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Acknowledgments

This study was supported by Grants from Beijing Key Laboratory of Metabolic Disorders Related Cardiovascular Disease Open Foundation of Capital Medical University (2014DXWL04) and Natural Sciences Foundation of China (NSFC) (81270283) to Huirong Liu.

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Authors and Affiliations

  1. Beijing Key Laboratory of Metabolic Disorders Related Cardiovascular Disease, Capital Medical University, Beijing, 100069, People’s Republic of China

    Ye Wu, Xin Liu, Huirong Liu & Xinliang Ma

  2. Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, No.10 Xitoutiao, You An Men, Beijing, 100069, People’s Republic of China

    Ye Wu, Xin Liu, Huirong Liu & Xinliang Ma

  3. Department of Biochemistry, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, 030001, Shanxi, People’s Republic of China

    Xiutao Tan

  4. Department of Pathophysiology, Ningxia Medical University, Yinchuan, 750004, Ningxia, People’s Republic of China

    Jue Tian

  5. Department of Physiology, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, 030001, Shanxi, People’s Republic of China

    Yehong Wang, Huanxin Zhao & Zi Yan

  6. Key Laboratory of Cellular Physiology (Shanxi Medical University), Ministry of Education, Taiyuan, 030001, People’s Republic of China

    Yehong Wang, Huanxin Zhao & Zi Yan

  7. Department of Emergency Medicine, Thomas Jefferson University, 1025 Walnut St, College Bldg 808, Philadelphia, PA, 19107, USA

    Xinliang Ma

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  1. Ye Wu
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  4. Xin Liu
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Correspondence to Huirong Liu or Xinliang Ma.

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Wu, Y., Tan, X., Tian, J. et al. PPARγ Agonist Ameliorates the Impaired Fluidity of the Myocardial Cell Membrane and Cardiac Injury in Hypercholesterolemic Rats. Cardiovasc Toxicol 17, 25–34 (2017). https://doi.org/10.1007/s12012-015-9352-9

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  • DOI: https://doi.org/10.1007/s12012-015-9352-9

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