Different secretion patterns of two molecular forms of cardiac adrenomedullin in pressure- and volume-overloaded human heart failure

Toshio Nishikimi, Hiroshi Asakawa, Hiroshi Iida, Yasushi Matsushita, Ikuko Shibasaki, Kazuyoshi Tadokoro, Yosuke Mori, Hideaki Mori, Yoshihiko Mochizuki, Yoshitaka Okamura, Shinichiro Miyoshi, Kenji Kangawa, Hiroaki Matsuoka

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Abstract

Background In the final step of production of adrenomedullin (AM), an inactive intermediate form of glycine-extended AM (AM-glycine) is converted to the active mature form of adrenomedullin (AM-mature) by enzymatic amidation. Recent studies have revealed that AM-mature and AM-glycine circulate in human plasma. In this study, we investigated the differences of the concentrations of cardiac AM between pressure-overloaded (PO) heart failure (HF) and volume-overloaded (VO)-HF in humans. Methods and results We measured AM-mature and AM-glycine by immunoradiometric assays in pericardial fluid and plasma in 38 patients who underwent valve replacement surgery (PO-HF: aortic stenosis, n=14; VO-HF: aortic or mitral regurgitation, n=24). Stable coronary artery disease with normal left ventricular function served as the control (n=24). Plasma AM-mature (VO-HF: +59%, PO-HF: +65%, P<.05) and AM-glycine (VO-HF: +43%, PO-HF: +50%, P<0.05) were similarly higher in the 2 HF groups than in the control group. Interestingly, pericardial fluid AM-mature was markedly higher than that in plasma (control: +789%, VO-HF: +1050%, PO-HF: +1745%, all P<.001). Pericardial fluid AM-mature was higher in VO-HF (+106%, P<.01) than in controls and they were further increased in PO-HF (+243%, P<.05). Pericardial fluid molecular forms of AM correlated with left ventricular systolic pressure, but not with left ventricular end-diastolic volume index in PO-HF. In contrast, they correlated with left ventricular end-diastolic volume index, but not with left ventricular systolic pressure in VO-HF. Conclusion These results suggest that cardiac AM is differently regulated from plasma AM and that cardiac AM production is upregulated in both types of HF in response to each different stimulus.

Original languageEnglish
Pages (from-to)321-327
Number of pages7
JournalJournal of Cardiac Failure
Volume10
Issue number4
DOIs
Publication statusPublished - Aug 1 2004

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Keywords

  • Adrenomedullin
  • Heart failure
  • Pericardial fluid
  • Plasma
  • Pressure overload
  • Valvular
  • Volume overload

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Nishikimi, T., Asakawa, H., Iida, H., Matsushita, Y., Shibasaki, I., Tadokoro, K., Mori, Y., Mori, H., Mochizuki, Y., Okamura, Y., Miyoshi, S., Kangawa, K., & Matsuoka, H. (2004). Different secretion patterns of two molecular forms of cardiac adrenomedullin in pressure- and volume-overloaded human heart failure. Journal of Cardiac Failure, 10(4), 321-327. https://doi.org/10.1016/j.cardfail.2003.12.002