title: Myocardial G protein receptor-coupled kinase expression correlates with functional parameters and clinical severity in advanced heart failure.
abstract: BACKGROUND
  In heart failure (HF), sympathetic hyperactivation induces deleterious effects in myocardial β-adrenergic signaling, with receptor down-regulation and desensitization mediated by G protein receptor-coupled kinases (GRKs). We hypothesised that changes in GRK isoforms may be associated with clinical status in advanced HF, using the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) scale.
  
  
  METHODS
  We included 31 patients with advanced HF undergoing transplantation. According to INTERMACS profiles, mRNA and protein levels of GRK isoforms in left ventricular (LV) myocardium were analyzed and compared with nonfailing LV samples.
  
  
  RESULTS
  In failing LV myocardium, GRK2 and GRK5 (but not GRK3) protein was up-regulated compared with control samples. Among HF patients, an increase in GRK2 and GRK5 mRNA and protein abundance was observed in β-agonist-treated patients (vs β-blockers: P < .05) and in higher-risk INTERMACS status (profiles 2 and 3 vs 4 and 5: P < .05). A significant negative correlation of GRK2 expression with LV stroke volume supported these findings.
  
  
  CONCLUSIONS
  Increased GRK2 correlates with clinical severity using the INTERMACS scale and LV stroke volume, supporting it as a potential target in advanced HF. These changes are paralleled by GRK5 expression in the failing myocardium, suggesting a relevant role in human HF.
authors.affiliation: Heart Failure and Transplant Unit, Department of Cardiology, La Fe University Hospital, Valencia, Spain. jaimeaguero30@hotmail.com
authors.forename: Jaime
authors.initials: J
authors.lastname: Agüero
authors.forename: Luis
authors.initials: L
authors.lastname: Almenar
authors.forename: Fermí
authors.initials: F
authors.lastname: Montó
authors.forename: Eduardo
authors.initials: E
authors.lastname: Oliver
authors.forename: Ignacio
authors.initials: I
authors.lastname: Sánchez-Lázaro
authors.forename: Diana
authors.initials: D
authors.lastname: Vicente
authors.forename: Luis
authors.initials: L
authors.lastname: Martínez-Dolz
authors.forename: Pilar
authors.initials: P
authors.lastname: D'Ocon
authors.forename: Joaquin
authors.initials: J
authors.lastname: Rueda
authors.forename: Antonio
authors.initials: A
authors.lastname: Salvador
mesh_terms: D015536:Down-Regulation; D005260:Female; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000235:genetics; D054774:G-Protein-Coupled Receptor Kinase 5 / Q000235:genetics; D054768:G-Protein-Coupled Receptor Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006333:Heart Failure / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology; D006353:Heart-Assist Devices; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D012042:Registries; D012720:Severity of Illness Index; D013030:Spain
chemical_list: D012333:RNA, Messenger; D054769:G-Protein-Coupled Receptor Kinase 2; D054774:G-Protein-Coupled Receptor Kinase 5; D054768:G-Protein-Coupled Receptor Kinases