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(Circulation. 2004;110:1787-1793.)
© 2004 American Heart Association, Inc.

Heart Failure

Possible Association of Heart Failure Status With Synthetic Balance Between Aldosterone and Dehydroepiandrosterone in Human Heart

Shota Nakamura, MD; Michihiro Yoshimura, MD, PhD; Masafumi Nakayama, MD, PhD; Teruhiko Ito, MD, PhD; Yuji Mizuno, MD, PhD; Eisaku Harada, MD, PhD; Tomohiro Sakamoto, MD, PhD; Yoshihiko Saito, MD, PhD; Kazuwa Nakao, MD, PhD; Hirofumi Yasue, MD, PhD; Hisao Ogawa, MD, PhD

From the Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University (S.N., M.Y., M.N., T.S., H.O.), Kumamoto, Japan; the Division of Cardiology, Kumamoto Aging Research Institute (T.I., Y.M., E.H., H.Y.), Kumamoto, Japan; the First Department of Internal Medicine, Nara Medical University (Y.S.), Nara, Japan; and the Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine (K.N.), Kyoto, Japan.

Correspondence to Dr Michihiro Yoshimura, Department of Cardiovascular Medicine, Graduate School of Medical Sciences, 1-1-1 Honjo, Kumamoto 860–8556, Japan. E-mail bnp{at}kumamoto-u.ac.jp

Received August 9, 2002; de novo received May 7, 2004; acepted June 17, 2004.

Background— Aldosterone is produced not only in the adrenal gland but also in the extra-adrenal tissues, including failing human heart. This study examined the production of dehydroepiandrosterone (DHEA) in human heart and elucidated the possible physiological significance.

Method and Results— Using left ventricular tissues obtained at autopsy, reverse transcription–polymerase chain reaction followed by Southern blot analysis revealed the gene expressions of CYP17. By measuring plasma aldosterone and DHEA levels at the coronary sinuses and aortic roots during cardiac catheterization, we found that DHEA but not aldosterone was secreted from control subjects (P<0.0001 and P=0.74, respectively), whereas aldosterone but not DHEA was secreted from patients with heart failure (P=0.0017 and P=0.67, respectively). To examine the significance of DHEA, we measured myocyte cell sizes and the gene expression of B-type natriuretic peptide (BNP), using a neonatal rat cardiocyte culture system. We found that DHEA (10^–8 mol/L) significantly inhibited the increase in myocyte cell sizes and BNP mRNA levels upregulated by endothelin-1 (P=0.031 and P<0.0001, respectively).

Conclusions— CYP17 gene expression and production of DHEA were demonstrated in human control heart. Also, we found that cardiac production of DHEA was suppressed in failing heart. We postulated that DHEA and/or its metabolites exert a cardioprotective action through antihypertrophic effects.

Key Words: heart failure • hormones • hypertrophy • cardiomyopathy • natriuretic peptides

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