title: Patients with Dilated Cardiomyopathy and Sustained Monomorphic Ventricular Tachycardia Show Up-Regulation of KCNN3 and KCNJ2 Genes and CACNG8-Linked Left Ventricular Dysfunction.
abstract: OBJECTIVE
  Disruptions in cardiac ion channels have shown to influence the impaired cardiac contraction in heart failure. We sought to determine the altered gene expression profile of this category in dilated cardiomyopathy (DCM) patients and relate the altered gene expression with the clinical signs present in our patients, such as ventricular dysfunction and sustained monomorphic ventricular tachycardia (SMVT).
  
  
  RESULTS
  Left ventricular (LV) tissue samples were used in RNA-sequencing technique to elucidate the transcriptomic changes of 13 DCM patients compared to controls (n = 10). We analyzed the differential gene expression of cardiac ion channels, and we found a total of 34 altered genes. We found that the calcium channel CACNG8 mRNA and protein levels were down-regulated and highly and inversely related with LV ejection fraction (LVEF) (r = -0.78, P<0.01). Furthermore, the potassium channels KCNN3 and KCNJ2 mRNA and protein levels were up-regulated and showed also a significant and inverse correlation with LVEF (r = -0.61, P<0.05; r = -0.60, P<0.05) in patients with SMVT.
  
  
  CONCLUSIONS
  A broad set of deregulated genes have been identified by RNA-sequencing technique. The relationship of CACNG8, KCNN3 and KCNJ2 with LVEF, and the up-regulation of KCNN3 and KCNJ2 in all patients with SMVT, irrespective of CACNG8 expression, suggest a significant role for these three ion flux related genes in the LV dysfunction present in this cardiomyopathy and an important relationship between KCNN3 and KCNJ2 up-regulation and the presence of SMVT.
authors.affiliation: Cardiocirculatory Unit, Health Research Institute of La Fe University Hospital (IIS La Fe), Valencia, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Ortega
authors.affiliation: Cardiocirculatory Unit, Health Research Institute of La Fe University Hospital (IIS La Fe), Valencia, Spain.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Tarazón
authors.affiliation: Cardiocirculatory Unit, Health Research Institute of La Fe University Hospital (IIS La Fe), Valencia, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Roselló-Lletí
authors.affiliation: Cardiocirculatory Unit, Health Research Institute of La Fe University Hospital (IIS La Fe), Valencia, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Gil-Cayuela
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: Jose-Ramón
authors.initials: JR
authors.lastname: González-Juanatey
authors.affiliation: Cardiology Service of Santa Creu i Sant Pau Hospital, Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Cinca
authors.affiliation: Cardiology Service of Santa Creu i Sant Pau Hospital, Barcelona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Jorge
authors.affiliation: Heart Failure and Transplantation Unit, Cardiology Department, La Fe University Hospital, Valencia, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Martínez-Dolz
authors.affiliation: Cardiocirculatory Unit, Health Research Institute of La Fe University Hospital (IIS La Fe), Valencia, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Portolés
authors.affiliation: Cardiocirculatory Unit, Health Research Institute of La Fe University Hospital (IIS La Fe), Valencia, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Rivera
mesh_terms: D015220:Calcium Channels / Q000235:genetics*; D002311:Cardiomyopathy, Dilated / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000235:genetics*; D017180:Tachycardia, Ventricular / Q000150:complications*; D015854:Up-Regulation; D018487:Ventricular Dysfunction, Left / Q000150:complications*
chemical_list: C521178:CACNG8 protein, human; D015220:Calcium Channels; C489457:KCNJ2 protein, human; C406328:KCNN3 protein, human; D024661:Potassium Channels, Inwardly Rectifying; D051640:Small-Conductance Calcium-Activated Potassium Channels