Aldosterone, but Not Angiotensin II, Reduces Angiotensin Converting Enzyme 2 Gene Expression Levels in Cultured Neonatal Rat Cardiomyocytes

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  • Yamamuro Megumi
    Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University
  • Yoshimura Michihiro
    Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine
  • Nakayama Masafumi
    Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University
  • Abe Koji
    Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University
  • Sumida Hitoshi
    Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University
  • Sugiyama Seigo
    Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University
  • Saito Yoshihiko
    First Department of Internal Medicine, Nara Medical University
  • Nakao Kazuwa
    Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine
  • Yasue Hirofumi
    Division of Cardiology, Kumamoto Aging Research Institute
  • Ogawa Hisao
    Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University

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Background A previous report showed that aldosterone upregulates angiotensin converting enzyme (ACE) gene expression levels in cultured neonatal rat cardiocytes. ACE2 is a novel homologue of ACE, which exists in the human heart, and ACE2 converts angiotensin I to angiotensin 1-9 and angiotensin II to angiotensin 1-7, thereby decreasing angiotensin II levels. In the present study, an investigation took place to see whether aldosterone regulates the expression of ACE2 as well as that of ACE in cultured neonatal rat cardiomyocytes. Methods and Results Primary neonatal rat cardiomyocytes were cultured with aldosterone. Total RNA was extracted from these cardiomyocytes and quantified the mRNA levels of ACE2, ACE and GAPDH by using real-time reverse transcription polymerase chain reaction analysis. Aldosterone significantly decreased ACE2 mRNA levels and increased ACE mRNA levels at 12 h. Angiotensin II, however, had no effect on either ACE2 mRNA levels or ACE mRNA levels. Eplerenone, a mineralocorticoid receptor antagonist, completely blocked the increase in ACE mRNA levels and the reduction in ACE2 mRNA levels due to aldosterone. Conclusion Aldosterone, but not angiotensin II, reduced ACE2 mRNA levels and increased ACE mRNA levels in rat cardiomyocytes via mineralocorticoid receptor. Aldosterone might play an important role in cardiac remodeling by upregulating ACE and downregulating ACE2 levels. (Circ J 2008; 72: 1346 - 1350)<br>

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  • Circulation Journal

    Circulation Journal 72 (8), 1346-1350, 2008

    一般社団法人 日本循環器学会

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