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Article

Decreased cardiac mitochondrial tetrahydrobiopterin in a rat model of pressure overload

  • Authors:
    • Shunichi Shimizu
    • Masaaki Ishibashi
    • Sumito Kumagai
    • Teruaki Wajima
    • Toshihito Hiroi
    • Tatsuya Kurihara
    • Masakazu Ishii
    • Yuji Kiuchi
  • View Affiliations / Copyright

    Affiliations: Department of Pathophysiology, Showa University School of Pharmacy, Tokyo 142-8555, Japan
  • Pages: 589-596
    |
    Published online on: January 10, 2013
       https://doi.org/10.3892/ijmm.2013.1236
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Abstract

Sustained cardiac pressure overload induces mitochondrial dysfunction and apoptosis of cardiomyocytes leading to pathological cardiac hypertrophy and dysfunction. Mitochondrial nitric oxide synthase (NOS) appears to cause uncoupling, which produces reactive oxygen species (ROS) instead of nitric oxide (NO), by a decrease in the cofactor tetrahydrobiopterin (BH4). This study focused on examining the changes in mitochondrial BH4 levels during cardiac pressure overload. Chronic cardiac pressure overload was generated by abdominal aortic banding in rats. Levels of BH4 and its oxidized form were measured in the mitochondria isolated from the left ventricle (LV) and the post-mitochondrial supernatants. Chronic aortic banding increased blood pressure, and induced cardiac hypertrophy and fibrosis. Notably, the BH4 levels were decreased while its oxidized forms were increased in LV mitochondria, but not in the post-mitochondrial supernatants containing the cytosol and microsome. Anti-neuronal NOS antibody-sensitive protein was detected in the cardiac mitochondria. Moreover, continuous administration of BH4 to rats with pressure overload increased mitochondrial BH4 levels and reduced cardiac fibrosis and matrix metallopeptidase activity, but not cardiac hypertrophy. These findings show the possibility that NOS uncoupling by decreased cardiac mitochondrial BH4 levels is implicated, at least in part, in the development of cardiac fibrosis, leading to cardiac dysfunction induced by pressure overload.
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Copy and paste a formatted citation
Spandidos Publications style
Shimizu S, Ishibashi M, Kumagai S, Wajima T, Hiroi T, Kurihara T, Ishii M and Kiuchi Y: Decreased cardiac mitochondrial tetrahydrobiopterin in a rat model of pressure overload. Int J Mol Med 31: 589-596, 2013.
APA
Shimizu, S., Ishibashi, M., Kumagai, S., Wajima, T., Hiroi, T., Kurihara, T. ... Kiuchi, Y. (2013). Decreased cardiac mitochondrial tetrahydrobiopterin in a rat model of pressure overload. International Journal of Molecular Medicine, 31, 589-596. https://doi.org/10.3892/ijmm.2013.1236
MLA
Shimizu, S., Ishibashi, M., Kumagai, S., Wajima, T., Hiroi, T., Kurihara, T., Ishii, M., Kiuchi, Y."Decreased cardiac mitochondrial tetrahydrobiopterin in a rat model of pressure overload". International Journal of Molecular Medicine 31.3 (2013): 589-596.
Chicago
Shimizu, S., Ishibashi, M., Kumagai, S., Wajima, T., Hiroi, T., Kurihara, T., Ishii, M., Kiuchi, Y."Decreased cardiac mitochondrial tetrahydrobiopterin in a rat model of pressure overload". International Journal of Molecular Medicine 31, no. 3 (2013): 589-596. https://doi.org/10.3892/ijmm.2013.1236
Copy and paste a formatted citation
x
Spandidos Publications style
Shimizu S, Ishibashi M, Kumagai S, Wajima T, Hiroi T, Kurihara T, Ishii M and Kiuchi Y: Decreased cardiac mitochondrial tetrahydrobiopterin in a rat model of pressure overload. Int J Mol Med 31: 589-596, 2013.
APA
Shimizu, S., Ishibashi, M., Kumagai, S., Wajima, T., Hiroi, T., Kurihara, T. ... Kiuchi, Y. (2013). Decreased cardiac mitochondrial tetrahydrobiopterin in a rat model of pressure overload. International Journal of Molecular Medicine, 31, 589-596. https://doi.org/10.3892/ijmm.2013.1236
MLA
Shimizu, S., Ishibashi, M., Kumagai, S., Wajima, T., Hiroi, T., Kurihara, T., Ishii, M., Kiuchi, Y."Decreased cardiac mitochondrial tetrahydrobiopterin in a rat model of pressure overload". International Journal of Molecular Medicine 31.3 (2013): 589-596.
Chicago
Shimizu, S., Ishibashi, M., Kumagai, S., Wajima, T., Hiroi, T., Kurihara, T., Ishii, M., Kiuchi, Y."Decreased cardiac mitochondrial tetrahydrobiopterin in a rat model of pressure overload". International Journal of Molecular Medicine 31, no. 3 (2013): 589-596. https://doi.org/10.3892/ijmm.2013.1236
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