title: 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.
  
  
  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.
authors.affiliation: Cardiocirculatory Unit, Instituto de Investigación Sanitaria Hospital Universitario La Fe, Valencia, Spain.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Tarazón
authors.affiliation: Cardiocirculatory Unit, Instituto de Investigación Sanitaria Hospital Universitario La Fe, Valencia, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Roselló-Lletí
authors.affiliation: Cardiocirculatory Unit, Instituto de Investigación Sanitaria Hospital Universitario La Fe, Valencia, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Rivera
authors.affiliation: Cardiocirculatory Unit, Instituto de Investigación Sanitaria Hospital Universitario La Fe, Valencia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Ortega
authors.affiliation: Cardiocirculatory Unit, Instituto de Investigación Sanitaria Hospital Universitario La Fe, Valencia, Spain.
authors.forename: Maria Micaela
authors.initials: MM
authors.lastname: Molina-Navarro
authors.affiliation: Sistemas Genómicos, Valencia, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Triviño
authors.affiliation: Cellular and Molecular Cardiology Research Unit, Department of Cardiology and Institute of Biomedical Research, University Clinical Hospital, Santiago de Compostela, Spain.
authors.forename: Francisca
authors.initials: F
authors.lastname: Lago
authors.affiliation: Cellular and Molecular Cardiology Research Unit, Department of Cardiology and Institute of Biomedical Research, University Clinical Hospital, Santiago de Compostela, Spain.
authors.forename: José Ramón
authors.initials: JR
authors.lastname: González-Juanatey
authors.affiliation: Cardiology Unit, Hospital San Francesc de Borja, Gandía, Spain.
authors.forename: Placido
authors.initials: P
authors.lastname: Orosa
authors.affiliation: Servicio de Cirugía Cardiovascular, Hospital Universitario La Fe, Valencia, Spain.
authors.forename: José Anastasio
authors.initials: JA
authors.lastname: Montero
authors.affiliation: Heart Failure and Transplantation Unit, Cardiology Department, Hospital Universitario La Fe, Valencia, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Salvador
authors.affiliation: Cardiocirculatory Unit, Instituto de Investigación Sanitaria Hospital Universitario La Fe, Valencia, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Portolés
mesh_terms: D000328:Adult; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism*; D002311:Cardiomyopathy, Dilated / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D045683:Furin / Q000378:metabolism; D015870:Gene Expression; D006333:Heart Failure / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D012697:Serine Endopeptidases / Q000378:metabolism
chemical_list: C472955:NPPA protein, human; D011498:Protein Precursors; D009320:Atrial Natriuretic Factor; C119812:CORIN protein, human; D012697:Serine Endopeptidases; C468731:FURIN protein, human; D045683:Furin