Dataset Information

RNA sequencing analysis and atrial natriuretic peptide production in patients with dilated and ischemic cardiomyopathy.

ABSTRACT:

Background

The atrium is the major site of ANP synthesis, which has been said to increase in heart failure as a result of increased production in the left ventricular (LV) myocardium. This is a key issue related to its diagnostic and prognostic capabilities. We aimed to evaluate protein levels of proANP and ANP and the enzymes that cleave the natriuretic peptides, corin and furin, in the LV tissue of heart transplant patients with dilated (DCM) and ischemic (ICM) cardiomyopathy compared with control donors (CNT). We also evaluate mRNA levels of ANP gene (NPPA) by RNA sequencing in the same tissue.

Methods and results

Seventy-three human LV tissue samples from ICM (n=30) and DCM (n=33) patients and CNT (n=10) were analyzed by Western blot and RNA sequencing. Comparing protein levels according to etiology, neither DCM nor ICM showed levels of proANP or ANP different from those of CNT. However, NPPA was increased in both groups compared to CNT (DCM 32 fold, p<0.0001; ICM 10 fold, p<0.0001). Corin (but not furin) was elevated in the ICM group compared to CNT (112 ± 24 vs. 100 ± 7, p<0.05), and its level was inversely related with LV ejection fraction (LVEF) (r=-0.399, p<0.05).

Conclusions

Patients present with elevated levels of NPPA but not of proANP or ANP proteins in LV tissue, which may be due to posttranscripcional regulation of NPPA or different pathways for ANP secretion between the atrium and ventricle. Moreover, there are differences between DCM and ICM in corin levels, indicating that a different molecular mechanism may exist that converge in this syndrome. Further, LV concentration of corin is inversely related to LVEF in ICM.

SUBMITTER: Tarazon E

PROVIDER: S-EPMC3943898 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

RNA sequencing analysis and atrial natriuretic peptide production in patients with dilated and ischemic cardiomyopathy.

Tarazón Estefanía E Roselló-Lletí Esther E Rivera Miguel M Ortega Ana A Molina-Navarro Maria Micaela MM Triviño Juan Carlos JC Lago Francisca F González-Juanatey José Ramón JR Orosa Placido P Montero José Anastasio JA Salvador Antonio A Portolés Manuel M

PloS one 20140305 3

<h4>Background</h4>The atrium is the major site of ANP synthesis, which has been said to increase in heart failure as a result of increased production in the left ventricular (LV) myocardium. This is a key issue related to its diagnostic and prognostic capabilities. We aimed to evaluate protein levels of proANP and ANP and the enzymes that cleave the natriuretic peptides, corin and furin, in the LV tissue of heart transplant patients with dilated (DCM) and ischemic (ICM) cardiomyopathy compared ...[more]

PMID: 24599027

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Project description:AimsMildly dilated cardiomyopathy (MDCM) was characterized as a subset of dilated cardiomyopathy (DCM) with systolic dysfunction and modest ventricular dilatation, of which the prognostic studies were limited. We aimed to compare the prognostic value of the N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hs-CRP) between MDCM and DCM.Methods and resultsWe retrospectively included hospitalized patients diagnosed with DCM and a left ventricular ejection fraction ≤ 50% at Fuwai Hospital from 2006 to 2017. MDCM was defined as left ventricular end-diastolic diameter index (LVEDDi) ≤ 33 mm/m2 in males and ≤34 mm/m2 in females. A total of 640 patients (median age 49 years, 24.8% female) were included in this study. At baseline, 110 cases (17%) were categorized as MDCM and 529 cases (83%) as DCM. Of 282 patients who had follow-up echocardiograms ≥ 6 months, 7 MDCM patients (11.1%) evolved to DCM and 70 DCM patients (32.0%) recovered to MDCM by the change of LVEDDi. Compared with DCM, patients with baseline MDCM had lower composite risks of all-cause mortality, heart transplantation, and heart failure rehospitalization [adjusted hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.43-0.93, P = 0.019]. Both hs-CRP and NT-proBNP were independently associated with the composite endpoint in the overall cohort (hs-CRP: adjusted HR 1.07, 95% CI 1.00-1.15, P = 0.036; NT-proBNP: adjusted HR 1.11, 95% CI 1.02-1.22, P = 0.019). After a propensity-score matching between MDCM and DCM, higher NT-proBNP (above the median) was significantly associated with the outcome in DCM patients (HR 1.83, 95% CI 1.05-3.20, P = 0.034), but not in MDCM patients (HR 1.54, 95% CI 0.76-3.11, P = 0.227). On the contrary, higher hs-CRP (above the median) showed prognostic value for adverse events in MDCM patients (HR 3.19, 95% CI 1.52-6.66, P = 0.002), but not in DCM patients (HR 1.04, 95% CI 0.61-1.79, P = 0.88).ConclusionsIn patients with MDCM, although no evidence suggested the prognostic role of NT-proBNP, higher level of hs-CRP was associated with outcome, supporting the use of hs-CRP in risk stratification for patients with MDCM.

Dataset Information

RNA sequencing analysis and atrial natriuretic peptide production in patients with dilated and ischemic cardiomyopathy.

Background

Methods and results

Conclusions

Publications

RNA sequencing analysis and atrial natriuretic peptide production in patients with dilated and ischemic cardiomyopathy.

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