Molecular forms of circulating adrenomedullin in patients with congestive heart failure

• Published in: Journal of endocrinology Vol. 160; no. 2; pp. 297 - 303
• Main Authors: Hirayama, N, Kitamura, K, Imamura, T, Kato, J, Koiwaya, Y, Tsuji, T, Kangawa, K, Eto, T
• Format: Journal Article
• Language: English
• Published: Colchester BioScientifica 01.02.1999; Portland Press
• Subjects: Adrenomedullin; Adult; Aged; Aged, 80 and over; Analysis of Variance; Atrial Natriuretic Factor - blood; Biological and medical sciences; Biomarkers - blood; Cardiology. Vascular system; Female; Heart; Heart Failure - blood; Heart Failure - physiopathology; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Humans; Male; Medical sciences; Middle Aged; Natriuretic Peptide, Brain - blood; Peptides - blood; Precipitin Tests; Pulmonary Wedge Pressure; Statistics, Nonparametric; Human; Heart failure; Molecular form; Investigation method; Pathophysiology; Heart disease; Peptide hormone; Adrenomedullin; Cardiovascular disease
• ISSN: 0022-0795; 1479-6805
• DOI: 10.1677/joe.0.1600297

In the biosynthesis of adrenomedullin (AM), an intermediate form, AM(1-52)-glycine-COOH (iAM), is cleaved from proAM and subsequently processed to a biologically active mature form, AM(1-52)-NH2 (mAM), by enzymatic amidation. We recently reported that immunoreactive AM in human plasma consists of mAM and iAM. To clarify the pathophysiological roles of mAM and iAM in heart failure, we established an assay method to specifically detect mAM, and we determined the plasma concentrations of mAM and iAM in 68 patients with congestive heart failure (CHF). The plasma mAM concentrations of the CHF patients classified as being class I or II of New York Heart Association (NYHA) functional classification were significantly greater than those of the 28 healthy controls, and a further increase was noted in the class III or IV patients. Similar increases in plasma iAM were also observed in these patients compared with controls. The increased plasma mAM and iAM in 12 patients with exacerbated CHF were significantly reduced by treatment of their CHF for 7 days. In addition, the plasma concentrations of both mAM and iAM were significantly correlated with pulmonary capillary wedge pressure, pulmonary artery pressure, right atrial pressure, cardiothoracic ratio, heart rate, and the plasma concentrations of atrial and brain natriuretic peptides in the CHF patients. Thus the plasma concentrations of both mAM and iAM were increased progressively in proportion to the severity of CHF. These results suggest that, though the role of iAM remains to be clarified, mAM acts against the further deterioration of heart failure in patients with CHF.