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


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.


CONCLUSIONS
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.
Department of Hypertension and Cardiorenal Medicine and Department of Thoracic Surgery, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
Toshio
T
Nishikimi
Hiroshi
H
Asakawa
Hiroshi
H
Iida
Yasushi
Y
Matsushita
Ikuko
I
Shibasaki
Kazuyoshi
K
Tadokoro
Yosuke
Y
Mori
Hideaki
H
Mori
Yoshihiko
Y
Mochizuki
Yoshitaka
Y
Okamura
Shinichiro
S
Miyoshi
Kenji
K
Kangawa
Hiroaki
H
Matsuoka
D053607:Adrenomedullin; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001021:Aortic Valve / Q000378:metabolism / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000502:physiology; D005260:Female; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D010496:Pericardium / Q000378:metabolism / Q000503:physiopathology; D013223:Statistics as Topic; D013318:Stroke Volume / Q000502:physiology*; D017725:Ventricular Pressure / Q000502:physiology*
D015415:Biomarkers; D010455:Peptides; D053607:Adrenomedullin