Augmented expression of atrial natriuretic polypeptide gene in ventricle of human failing heart.
To elucidate the expression of the atrial natriuretic polypeptide (ANP) gene in the ventricle of the human failing heart, we have measured ANP and ANP messenger RNA (ANPmRNA) levels in left ventricular aneurysm obtained at operation, biopsy specimens of left ventricles from dilated cardiomyopathy (DCM) and autopsy samples of old myocardial infarction (OMI) and DCM hearts, and compared the levels with those in the normal ventricle. The ANP level (mean +/- SE) was 17.5 +/- 6.9 ng/g in the normal ventricle, and increased to 660.3 +/- 122.2 ng/g in the left ventricular aneurysm tissues and to 3,138.6 +/- 1,642.1 ng/g in the biopsy specimens of the DCM ventricle. These levels were approximately 40 and 200 times higher than in the normal ventricle. The increase of ANP levels was observed in both infarcted and noninfarcted regions of the OMI heart, and in the entire ventricle of the DCM heart. A significant positive correlation was found between the ANP level in aneurysm tissues and pulmonary capillary wedge pressure (r = 0.85). The ANPmRNA level in the left ventricular aneurysm showed about a 10-fold increase compared with that in the normal heart and reached 23% of that in the atrium of the same heart. A similar increase in the ANPmRNA level was observed in the entire ventricle of DCM. These data clearly indicate that the expression of the ANP gene in the ventricle is augmented in the failing heart in accordance with the severity of heart failure. In the atrium of the failing heart, ANP and ANPmRNA levels were only two times higher than those in the normal atrium. Thus, the augmentation in the expression of the ANP gene was more prominent in the ventricle than in the atrium. Taking tissue weight into account, the total content of ANPmRNA in the ventricle of the failing heart is much the same as that in the normal atrium. The ratio of the ANP level to the ANPmRNA level in the ventricle is much smaller than that in the atrium. These results suggest more rapid secretion of ANP after synthesis in the ventricle. These findings demonstrate that the expression of the ANP gene is augmented in the human ventricle of the failing heart and suggest that the ventricle becomes a substantial source of circulating ANP in congestive heart failure.
Saito
Y
Y
Department of Medicine, Kyoto University School of Medicine, Japan.
Nakao
K
K
Arai
H
H
Nishimura
K
K
Okumura
K
K
Obata
K
K
Takemura
G
G
Fujiwara
H
H
Sugawara
A
A
Yamada
T
T
D000368:Aged; D009320:Atrial Natriuretic Factor / Q000235:genetics*; D015152:Blotting, Northern; D005260:Female; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000235:genetics* / Q000378:metabolism; D006352:Heart Ventricles / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis
D012333:RNA, Messenger; D009320:Atrial Natriuretic Factor