Metabolic remodeling in the right ventricle of rats with severe pulmonary arterial hypertension

  • Authors:
    • Seiichiro Sakao
    • Eiryo Kawakami
    • Hiroki Shoji
    • Akira Naito
    • Hideki Miwa
    • Rika Suda
    • Takayuki Jujo Sanada
    • Nobuhiro Tanabe
    • Koichiro Tatsumi
  • View Affiliations

  • Published online on: January 25, 2021     https://doi.org/10.3892/mmr.2021.11866
  • Article Number: 227
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Abstract

It is generally considered that there is an increase in glycolysis in the hypertrophied right ventricle (RV) during pulmonary hypertension (PH), which leads to a decrease in glucose oxidation through the tricarboxylic acid (TCA) cycle. Although recent studies have demonstrated that fatty acid (FA) and glucose accumulated in the RV of patients with PH, the details of this remain to be elucidated. The purpose of the current study was to assess the metabolic remodeling in the RV of rats with PH using a metabolic analysis. Male rats were treated with the vascular endothelial growth factor receptor blocker SU5416 followed by 3 weeks of hypoxic conditions and 5 weeks of normoxic conditions (Su/Hx rats). Hemodynamic measurements were conducted, and the RV was harvested for the measurement of metabolites. A metabolomics analysis revealed a decreasing trend in the levels of alanine, argininosuccinic acid and downstream TCA cycle intermediates, including fumaric and malic acid and an increasing trend in branched‑chain amino acids (BCAAs) in Su/Hx rats compared with the controls; however, no trends in glycolysis were indicated. The FA metabolomics analysis also revealed a decreasing trend in the levels of long‑chain acylcarnitines, which transport FA from the cytosol to the mitochondria and are essential for beta‑oxidation. The current study demonstrated that the TCA cycle was less activated because of a decreasing trend in the expression of fumaric acid and malic acid, which might be attributable to the expression of adenylosuccinic acid and argininosuccinic acid. These results suggest that dysregulated BCAA metabolism and a decrease in FA oxidation might contribute to the reduction of the TCA cycle reactions.
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April-2021
Volume 23 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Sakao S, Kawakami E, Shoji H, Naito A, Miwa H, Suda R, Sanada TJ, Tanabe N and Tatsumi K: Metabolic remodeling in the right ventricle of rats with severe pulmonary arterial hypertension. Mol Med Rep 23: 227, 2021
APA
Sakao, S., Kawakami, E., Shoji, H., Naito, A., Miwa, H., Suda, R. ... Tatsumi, K. (2021). Metabolic remodeling in the right ventricle of rats with severe pulmonary arterial hypertension. Molecular Medicine Reports, 23, 227. https://doi.org/10.3892/mmr.2021.11866
MLA
Sakao, S., Kawakami, E., Shoji, H., Naito, A., Miwa, H., Suda, R., Sanada, T. J., Tanabe, N., Tatsumi, K."Metabolic remodeling in the right ventricle of rats with severe pulmonary arterial hypertension". Molecular Medicine Reports 23.4 (2021): 227.
Chicago
Sakao, S., Kawakami, E., Shoji, H., Naito, A., Miwa, H., Suda, R., Sanada, T. J., Tanabe, N., Tatsumi, K."Metabolic remodeling in the right ventricle of rats with severe pulmonary arterial hypertension". Molecular Medicine Reports 23, no. 4 (2021): 227. https://doi.org/10.3892/mmr.2021.11866