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January 1, 1989Journal of Clinical Investigation240 citationsOpen Access

Augmented expression of atrial natriuretic polypeptide gene in ventricle of human failing heart.

YSYoshihiko SaitoKNKazuwa NakaoHAHiroshi Arai

Key Result

In human failing hearts, ventricular atrial natriuretic polypeptide levels were 40 to 200 times higher than in normal ventricles, demonstrating augmented ANP gene expression in congestive heart failure.

Key Points

  • The aim is to investigate the expression levels of the atrial natriuretic polypeptide gene in the ventricles of failing human hearts.
  • Measured ANP and ANPmRNA levels in left ventricular aneurysm, DCM, and OMI tissues.
  • Compared these levels with those in normal ventricle samples.
  • Observed correlations with pulmonary capillary wedge pressure.
  • ANP levels in normal ventricle were 17.5 ng/g, rising to 660.3 ng/g in aneurysm tissues and 3,138.6 ng/g in DCM specimens.
  • ANPmRNA in left ventricular aneurysm increased approximately 10-fold compared to normal heart, reaching 23% of atrial levels.
  • A significant correlation (r = 0.85) was noted between ANP levels and pulmonary capillary wedge pressure.

Study Design

Type

Observational (n=24)

Multicenter

Yes

Structured PICO

P
Population
24 human subjects (14 with congestive heart failure [CHF] and 10 without CHF), mean age 62.1 years, 18 men and 6 women. CHF causes included antero-septal old myocardial infarction (OMI) (n=8), inferior OMI (n=1), and dilated cardiomyopathy (DCM) (n=5). Non-CHF subjects included 5 with coronary artery disease and 5 autopsied patients without cardiac complications.
C
Comparator
Normal heart tissue from patients without CHF
O
Outcome
Atrial natriuretic polypeptide (ANP) and ANP messenger RNA (ANPmRNA) levels in ventricular tissuesurrogate

The expression of the ANP gene is markedly augmented in the human ventricle of the failing heart, suggesting the ventricle becomes a substantial source of circulating ANP in congestive heart failure.

Main Result

Absolute Event Rate: 660.3% vs 17.5%

Limitations

  • Small sample size
  • Potential for postmortem RNA and peptide degradation in autopsy samples

Abstract

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.

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Cite This Study

Saito et al. (1989) conducted an observational in Congestive heart failure (n=24). Congestive heart failure vs. Normal cardiac function was evaluated on Ventricular atrial natriuretic polypeptide (ANP) level (ng/g). In human failing hearts, ventricular atrial natriuretic polypeptide levels were 40 to 200 times higher than in normal ventricles, demonstrating augmented ANP gene expression in congestive heart failure.

synapsesocial.com/papers/6a0d514568ddba849a09b291https://doi.org/10.1172/jci113872
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