Dataset Information

Role of B-type natriuretic peptide in epoxyeicosatrienoic acid-mediated improved post-ischaemic recovery of heart contractile function.

ABSTRACT:

Aims

This study examined the functional role of B-type natriuretic peptide (BNP) in epoxyeicosatrienoic acid (EET)-mediated cardioprotection in mice with targeted disruption of the sEH or Ephx2 gene (sEH null).

Methods and results

Isolated mouse hearts were perfused in the Langendorff mode and subjected to global no-flow ischaemia followed by reperfusion. Hearts were analysed for recovery of left ventricular developed pressure (LVDP), mRNA levels, and protein expression. Naïve hearts from sEH null mice had similar expression of preproBNP (Nppb) mRNA compared with wild-type (WT) hearts. However, significant increases in Nppb mRNA and BNP protein expression occurred during post-ischaemic reperfusion and correlated with improved post-ischaemic recovery of LVDP. Perfusion with the putative EET receptor antagonist 14,15-epoxyeicosa-5(Z)-enoic acid prior to ischaemia reduced the preproBNP mRNA in sEH null hearts. Inhibitor studies demonstrated that perfusion with the natriuretic peptide receptor type-A (NPR-A) antagonist, A71915, limited the improved recovery in recombinant full-length mouse BNP (rBNP)- and 11,12-EET-perfused hearts as well as in sEH null mice. Increased expression of phosphorylated protein kinase C epsilon and Akt were found in WT hearts perfused with either 11,12-EET or rBNP, while mitochondrial glycogen synthase kinase-3beta was significantly lower in the same samples. Furthermore, treatment with the phosphoinositide 3-kinase (PI3K) inhibitor wortmannin abolished improved LVDP recovery in 11,12-EET-treated hearts but not did significantly inhibit recovery of rBNP-treated hearts.

Conclusion

Taken together, these data indicate that EET-mediated cardioprotection involves BNP and PI3K signalling events.

SUBMITTER: Chaudhary KR

PROVIDER: S-EPMC2701722 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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Publications

Role of B-type natriuretic peptide in epoxyeicosatrienoic acid-mediated improved post-ischaemic recovery of heart contractile function.

Chaudhary Ketul R KR Batchu Sri Nagarjun SN Das Dipankar D Suresh Mavanur R MR Falck John R JR Graves Joan P JP Zeldin Darryl C DC Seubert John M JM

Cardiovascular research 20090428 2

<h4>Aims</h4>This study examined the functional role of B-type natriuretic peptide (BNP) in epoxyeicosatrienoic acid (EET)-mediated cardioprotection in mice with targeted disruption of the sEH or Ephx2 gene (sEH null).<h4>Methods and results</h4>Isolated mouse hearts were perfused in the Langendorff mode and subjected to global no-flow ischaemia followed by reperfusion. Hearts were analysed for recovery of left ventricular developed pressure (LVDP), mRNA levels, and protein expression. Naïve hea ...[more]

PMID: 19401302

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Project description:AimsThe methodology to distinguish between the heart failure (HF) with recovered ejection fraction (HFrecEF) and those with continuously reduced ejection fraction (EF) (HFcrEF) on admission has not been established. We recently demonstrated that the ratio of plasma levels of pro-B-type natriuretic peptide (proBNP) to total BNP (proBNP plus mature BNP) is decreased on admission in patients with mild acute HF, but not in severe acute HF as a compensatory mechanism for activating cyclic GMP via increases of bioactive mature BNP. We aimed to test the hypothesis that the ratio of bioactive mature BNP to total BNP is associated with reverse remodelling capacity in patients with HF with reduced EF.Methods and resultsPlasma proBNP and total BNP were measured in patients with acute decompensated HF by using specific and sensitive enzyme immunochemiluminescent assay. Estimated percent mature BNP (%emBNP) was calculated as ([total BNP - proBNP]/total BNP) × 100. We retrospectively identified the patients with reduced EF (≤40%, on admission) who had echocardiographic data after discharge (n = 93). We defined patients with increased EF by >10% during the follow-up term (median, 545 days) after the admission as HFrecEF group. We compared patient characteristics, %emBNP, and other biomarkers between HFrecEF and HFcrEF. Of the enrolled patients with HFrecEF (n = 32) and HFcrEF (n = 61), on admission, %emBNP was significantly higher in HFrecEF than in HFcrEF (44.1% vs. 36.9%; P < 0.05). There were no significant differences in left ventricular EF on admission between the two groups. The univariate analysis revealed that %emBNP on admission was associated with HFrecEF occurrence rate (P < 0.05), in contrast both total BNP and high-sensitive cardiac troponin-T levels were not associated with HFrecEF occurrence rate.ConclusionsThe ratio of mature BNP to total BNP in plasma at the time of hospital admission may be predictive of left ventricular contractile recovery. Preservation of the capacity to convert proBNP to mature BNP, but not myocardial injury itself, is associated with future ventricular contractile recovery.

Project description:OBJECTIVES:Anaemia is a risk of worsening heart failure. However, anaemia sometimes remains undetected because the superficial cardiac function does not precisely reflect the adverse impact of anaemia. Plasma B-type natriuretic peptide (BNP) could be helpful in these cases. However, the direct anaemic effects on BNP remain unknown. Herein, we compared the direct effect of anaemia on BNP and left ventricular ejection fraction (LVEF) using an advanced statistical procedure. DESIGN:A retrospective study. SETTING:Secondary care (cardiology), single-centre study. PARTICIPANTS:The study consisted of 3756 inpatients, including 684 without ischaemic heart disease (IHD) and 3072 with IHD. PRIMARY AND SECONDARY OUTCOME MEASURES:Relationship between plasma BNP levels and LVEF values. RESULTS:A path model was constructed to simultaneously examine the adverse impact of anaemia on LVEF and plasma BNP, allowing for renal function. The path model revealed that LVEF increased in response to low haemoglobin (Hb), and the phenomenon was prominent in non-IHD (standardised regression coefficients (St.β): -0.264, p<0.001) rather than in IHD (St.β: 0.015, p=0.531). However, the response of BNP was commonly observed in both groups (non-IHD St.β: -0.238, IHD St.β: -0.398, p<0.001, respectively). Additionally, this study showed a direct link between low estimated glomerular filtration rate and high BNP independently of LVEF. Incrementally, Bayesian structural equation modelling in covariance structure analysis clearly supported this result. The scatter plots and simple regression analysis revealed that an adequate blood supply was approximately Hb 110 g/L and over in the non-IHD patients, whereas blood was not supplied in sufficient quantities even by Hb 130 g/L in patients with IHD. CONCLUSION:The current study demonstrated that anaemia was a substantial risk for worsening cardiac overload as estimated by plasma BNP. The anaemic response of LVEF likely changed depending on underlying cardiac disorders (IHD or not). However, the response of BNP was robustly observed.

Project description:ObjectivesThe purpose of this study was to assess whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels differ according to race/ethnicity.BackgroundNatriuretic peptides (NP) are hormones with natriuretic, diuretic, and vasodilatory effects. Experimental NP deficiency promotes salt-sensitive hypertension and cardiac hypertrophy, conditions that are more common among black individuals.MethodsWe examined plasma NT-proBNP levels according to race/ethnicity in 3,148 individuals (51% black, 31% white, 18% Hispanic) free of prevalent cardiovascular disease in the Dallas Heart Study. NT-proBNP values in the bottom sex-specific quartile were defined as low. Multivariable linear and logistic regression analyses were performed adjusting for clinical covariates and magnetic resonance imaging measurements of cardiac structure and function.ResultsHypertension was present in 41%, 25%, and 16% of black, white, and Hispanic individuals, respectively. Unadjusted NT-proBNP levels were lowest in black (median: 24 pg/ml; interquartile range [IQR]: 10 to 52 pg/ml) as compared with Hispanic (30 pg/ml; IQR: 14 to 59 pg/ml) and white individuals (32 pg/ml; IQR: 16 to 62 pg/ml), p < 0.0001. In multivariable-adjusted models, black individuals still had significantly lower NT-proBNP levels (-39% [95% confidence interval: -46% to -31%]; p < 0.0001) and greater odds of having low NT-proBNP (odds ratio: 2.46 [95% confidence interval: 1.86 to 3.26]), compared with white individuals. In contrast, NT-proBNP levels did not significantly differ between Hispanic and white individuals (p = 0.28). The finding of lower NT-proBNP levels in black individuals was similar when analyses were restricted to healthy participants without cardiovascular risk factors.ConclusionsIn this multiethnic cohort, NT-proBNP levels differ substantially according to race/ethnicity. Despite a higher prevalence of hypertension, black individuals had significantly lower NP levels than white and Hispanic individuals. A relative NP "deficiency" among black individuals may lead to greater susceptibility to salt retention and hypertension.

Project description:ObjectivesThis study was conducted to determine whether urinary excretion of C-type natriuretic peptide (CNP) is elevated in acute decompensated heart failure (ADHF) and whether elevated levels predict adverse outcomes.BackgroundUrinary CNP has been detected in patients with heart failure, but its clinical significance and prognostic utility, compared to established kidney injury biomarkers, in ADHF is unknown.MethodsWe measured 24-h urinary excretion and concurrent plasma concentrations of CNP22, CNP53, and NT-CNP53 in 58 ADHF patients and 20 healthy control subjects. Urinary kidney injury molecule (KIM)-1 and neutrophil gelatinase–associated lipocalin (NGAL) and plasma N-terminal pro-B type natriuretic peptide (NT-proBNP) were also measured. Mortality and all-cause rehospitalization/death were assessed over a follow-up of 1.5 ± 0.9 years.ResultsADHF patients had higher urinary excretion of all 3 CNP molecular forms than did controls. Plasma CNP22 and CNP53 were elevated in ADHF but showed limited correlation with urinary excretion, suggesting that mainly renal-derived CNP appears in urine. Plasma NT-proBNP and urinary KIM-1 were also elevated in ADHF (p < 0.0001); urinary NGAL was similar to that in controls. At 6 months, event-free survival values in ADHF patients were 86% for mortality and 59% for all-cause rehospitalization/death. On Cox regression analysis, urinary NT-CNP53 was the only predictor of mortality (hazard ratio: 1.7; 95% confidence interval: 1.1 to 2.4; p = 0.01) and all-cause rehospitalization/death (hazard ratio: 1.8; 95% confidence interval: 1.3 to 2.4; p = 0.0004), even after adjustment. Integrated discrimination analysis suggested that urinary NT-CNP53 combined with plasma NT-proBNP improved the prediction of adverse outcomes.ConclusionsThe findings from this study support the clinical utility of urinary CNP molecular forms. In ADHF, urinary NT-CNP53 correlated with prognosis, better predicted outcomes than did urinary NGAL and KIM-1, and improved the prognostic value of plasma NT-proBNP.

Dataset Information

Role of B-type natriuretic peptide in epoxyeicosatrienoic acid-mediated improved post-ischaemic recovery of heart contractile function.

Aims

Methods and results

Conclusion

Publications

Role of B-type natriuretic peptide in epoxyeicosatrienoic acid-mediated improved post-ischaemic recovery of heart contractile function.

Similar Datasets

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