&lt;b&gt;Cyclic GMP Production by ANP, BNP, and NO during Worsening and Improvement of Chronic Heart Failure&lt;/b&gt;

Takahashi, Motoi; Takeda, Sadao; Kurokawa, Syuhei; Kubo, Takaaki; Fukuda, Naoto; Izumi, Tohru

doi:10.1536/jhj.44.713

Cited by 15 publications

(15 citation statements)

References 23 publications

(21 reference statements)

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“…8, 28 Plasma ANP and BNP levels were significantly elevated at terminal Stage D HF corresponding to 20 weeks. Consistent with clinical reports for overt HF 15, 20, 29 cGMP levels were elevated at Stage C and D of HF in DCM. While plasma cGMP levels are positively associated with plasma immunoreactive ANP or BNP, NP system activation appears insufficient to attenuate the decline in systolic function and transition to terminal HF.…”

Section: Discussionsupporting

confidence: 89%

“…NP signaling is an important, but not sole determinant of circulating cGMP. 29 cGMP is an intracellular second messenger for nitric oxide (NO) 30 which is also elevated in chronic human HF. 29 It has been suggested that cGMP is produced mainly by NO in humans with chronic HF requiring hospitalization, but as HF improves and the patient nears discharge, NO is primarily produced by ANP and BNP.…”

Section: Discussionmentioning

confidence: 99%

“…29 It has been suggested that cGMP is produced mainly by NO in humans with chronic HF requiring hospitalization, but as HF improves and the patient nears discharge, NO is primarily produced by ANP and BNP. 29 …”

Section: Discussionmentioning

confidence: 99%

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Depressed Corin Levels Indicate Early Systolic Dysfunction Before Increases of Atrial Natriuretic Peptide/B-Type Natriuretic Peptide and Heart Failure Development

et al. 2016

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Dilated cardiomyopathy is a major cause of heart failure that affects millions. Corin cleaves and biologically activates pro-atrial natriuretic peptide (pro-ANP) and pro-B-type natriuretic peptide (pro-BNP). High corin levels reduce the development of systolic dysfunction and heart failure in experimental dilated cardiomyopathy. Yet, patients with significant heart failure unexpectedly show low corin levels with high plasma ANP/BNP levels. Therefore, we examined the relationship between cardiac corin expression, ANP/BNP levels and the stages of heart failure. We used a well-established, dilated cardiomyopathy model to evaluate gene and protein expression as mice longitudinally developed Stages A-D heart failure. Cardiac systolic function (ejection fraction) continuously declined over time (P<0.001). Cardiac corin transcripts were decreased at early Stage B heart failure and remained low through Stages C-D (P<0.001). Cardiac corin levels were positively correlated with systolic function (r=0.96, P=0.003) and inversely with lung water (r=-0.92, P=0.001). In contrast, cardiac pro-ANP/BNP transcripts increased later (Stage C-D) and plasma levels rose only with terminal heart failure (Stage D, P<0.001). Immunoreactive plasma ANP and BNP levels were positively associated with plasma cyclic guanosine monophosphate (cGMP) levels (r=0.82, P=0.01 & r=0.8, P=0.02 respectively). In experimental dilated cardiomyopathy, corin levels declined early with progressive systolic dysfunction before the development of heart failure, while significant increases in plasma ANP, BNP and cGMP levels were found only in later Stage (C, D) heart failure. This dyssynchrony in expression of corin vs. ANP/BNP may impair cleavage-activation of pro-natriuretic peptides and thereby promote the transition from earlier to later stage heart failure.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

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Depressed Corin Levels Indicate Early Systolic Dysfunction Before Increases of Atrial Natriuretic Peptide/B-Type Natriuretic Peptide and Heart Failure Development

et al. 2016

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“…Indeed, the severity of heart failure is linked to levels of ANP-related peptides 34–36 . While patients with severe heart failure develop high levels of ANP-related peptides and high levels of cGMP, our study and others have shown that there is no correlation between cGMP levels and total ANP-related peptides 5, 37 . We postulated that one explanation for the loss of the relationship between levels of ANP-related peptides and cGMP could be that corin levels and pro-ANP cleavage were reduced in severe heart failure.…”

Section: Discussioncontrasting

confidence: 68%

Decompensated Heart Failure Is Associated With Reduced Corin Levels and Decreased Cleavage of Pro–Atrial Natriuretic Peptide

Ibebuogu

Gladysheva

Houng

et al. 2011

Circ: Heart Failure

118

117

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Background By promoting salt and water excretion, the corin and the atrial natriuretic peptide (ANP) system should help to maintain fluid balance in heart failure. Yet, the development of fluid retention despite high levels of ANP-related peptides, suggests that this compensatory system is limited. Methods and Results Levels of circulating corin (the pro-ANP converting enzyme) and pro-ANP were measured in hospitalized patients with heart failure, using novel immunoassays. Patients (n = 14) had severe heart failure (NYHA class III–IV) with a median ejection fraction of 18 % and median BNP levels of 1940 pg/ml. In heart failure, median plasma corin levels were 7.6-fold lower than measured in plasma from 16 normal controls (180 vs. 1368 pg/ml, p<0.01). In contrast, in heart failure patients, levels of plasma N-terminal ANP peptides (N-ANP and pro-ANP) levels were markedly elevated (42.0 vs. 7.5 ng/ml, p<0.01). Levels of uncleaved pro-ANP, measured by novel immunoassays, were significantly higher in heart failure patients (p < 0.01) suggesting that corin cleavage of pro-ANP was impaired. Median plasma levels of cGMP were elevated in heart failure patients (150.0 vs. 7.6 pmol/ml, p<0.01) and plasma cGMP levels positively correlated with the fractional amount of cleaved pro-ANP (rs = 0.59, p < 0.03) but not with levels of uncleaved pro-ANP, implying that the cellular response to ANP remained intact. Conclusions Taken together these data suggest that there may be patients for whom low corin levels and impaired pro-ANP cleavage contribute to acute decompensation.

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“…Plasma cGMP, which is produced by activation of NPR-A and its cGMP cyclase, is a useful biomarker, reflecting the biological activity of ANP and BNP in vivo. In a study of patients with acutely decompensated HF, iANP and iBNP were shown to increase significantly as symptoms worsened and to decrease as symptoms resolved 33. However, cGMP levels at the worsening and improving phases remained unchanged.…”

Section: Clinical Implications Of Molecular Forms Of Natriuretic Peptmentioning

confidence: 96%

Molecular forms of natriuretic peptides in heart failure and their implications

Xu-Cai

2009

Heart

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<b>Cyclic GMP Production by ANP, BNP, and NO during Worsening and Improvement of Chronic Heart Failure</b>

Cited by 15 publications

References 23 publications

Depressed Corin Levels Indicate Early Systolic Dysfunction Before Increases of Atrial Natriuretic Peptide/B-Type Natriuretic Peptide and Heart Failure Development

Depressed Corin Levels Indicate Early Systolic Dysfunction Before Increases of Atrial Natriuretic Peptide/B-Type Natriuretic Peptide and Heart Failure Development

Decompensated Heart Failure Is Associated With Reduced Corin Levels and Decreased Cleavage of Pro–Atrial Natriuretic Peptide

Molecular forms of natriuretic peptides in heart failure and their implications

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