title: Down-regulation of cardioprotective bradykinin type-2 receptors in the left ventricle of patients with end-stage heart failure.
abstract: OBJECTIVE
  We sought to study the expression of bradykinin type-2 receptors (BK-2Rs) in patients with heart failure (HF).
  
  
  BACKGROUND
  Recent work in experimental animals has suggested that bradykinin (BK) exerts cardioprotective effects through specific BK-2Rs. However, nothing is known about the regulation of BK-2R expression in the pathogenesis of human HF.
  
  
  METHODS
  Human heart tissue was obtained from excised hearts of patients undergoing cardiac transplantation (n = 13) and from normal hearts (n = 6) unsuitable for donation. The patients had HF due to idiopathic dilated cardiomyopathy (IDC) (n = 7) or coronary heart disease (CHD) (n = 6). Tissue samples from the left ventricles were analyzed by competitive reverse-transcriptase-polymerase chain reaction and Western blotting for the expression of BK-2R messenger ribonucleic acid (mRNA) and protein.
  
  
  RESULTS
  In both the IDC and CHD hearts, the level of BK-2R mRNA expression was found to be significantly lower (30% and 38% of control values, respectively) than that in normal hearts. Correspondingly, the BK-2R protein level was significantly reduced in both the IDC and CHD hearts (45% and 62% of control values, respectively) and apparently involved all myocardial cell types. The down-regulation of BK-2R expression in failing hearts did not correlate with decreased cellularity or with the expression pattern of other members of the G-protein-coupled receptor superfamily. However, BK-2R down-regulation in the failing hearts was associated with a decrease in endothelial nitric oxide synthase in both IDC (53% of control value) and CHD (43% of control value) hearts.
  
  
  CONCLUSIONS
  These results are the first to suggest that a loss of BK-2Rs is involved in the pathogenesis of human HF.
authors.affiliation: Wihuri Research Institute, Helsinki, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Kuoppala
authors.forename: Naotaka
authors.initials: N
authors.lastname: Shiota
authors.forename: Jorma O
authors.initials: JO
authors.lastname: Kokkonen
authors.forename: Inka
authors.initials: I
authors.lastname: Liesmaa
authors.forename: Karam
authors.initials: K
authors.lastname: Kostner
authors.forename: Mikko
authors.initials: M
authors.lastname: Mäyränpää
authors.forename: Petri T
authors.initials: PT
authors.lastname: Kovanen
authors.forename: Ken A
authors.initials: KA
authors.lastname: Lindstedt
mesh_terms: D000328:Adult; D015153:Blotting, Western; D002311:Cardiomyopathy, Dilated / Q000378:metabolism; D003327:Coronary Disease / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III; D012333:RNA, Messenger / Q000235:genetics; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016277:Ventricular Function, Left / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D043782:Receptor, Bradykinin B2; D018002:Receptors, Bradykinin; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III