title: Patients with end-stage congestive heart failure treated with beta-adrenergic receptor antagonists have improved ventricular myocyte calcium regulatory protein abundance.
abstract: BACKGROUND
  Alterations in Ca(2+)-handling proteins are thought to underlie the deranged Ca(2+) transients that contribute to deterioration of cardiac function in congestive heart failure (CHF). Clinical trials in CHF patients have shown that treatment with beta-adrenergic receptor antagonists (betaB) improves cardiac performance. The present study determined whether the abundance of Ca(2+)-handling proteins is different in failing hearts from patients treated or untreated with beta B.
  
  
  RESULTS
  Ca(2+) regulatory protein abundance was compared in LV myocardium of 10 nonfailing hearts (NF group) and 44 failing hearts (CHF group) removed at transplantation. Analysis was performed in betaB-treated (betaB-CHF) and non-betaB treated (non-betaB-CHF) patients and in 4 subgroups: ischemic cardiomyopathy (ICM, n=10), nonischemic dilated cardiomyopathy (DCM, n=10), ICM with betaB therapy (betaB-ICM, n=12), and DCM with betaB therapy (betaB-DCM, n=12). Sarcoplasmic reticulum Ca(2+) ATPase, phospholamban, and Na(+)-Ca(2+) exchanger protein abundance were determined by use of Western blot analysis. Ca(2+) transients were measured with fluo-3. Sarcoplasmic reticulum Ca(2+) ATPase was significantly less abundant whereas phospholamban and Na(+)-Ca(2+) exchanger were not significantly altered in non-betaB-CHF versus NF. Sarcoplasmic reticulum Ca(2+) ATPase in the betaB-ICM and betaB-DCM was greater than in non-betaB-CHF and were not different than in NF. Ca(2+) transients in non-betaB-CHF myocytes had significantly smaller peaks and were prolonged versus NF myocytes. Ca(2+) transients from betaB-CHF myocytes had shorter durations than in betaB-CHF myocytes.
  
  
  CONCLUSIONS
  betaB treatment in CHF patients can normalize the abundance of myocyte Ca(2+) regulatory proteins and improve Ca(2+)-handling.
authors.affiliation: Cardiovascular Research Group, Department of Physiology and Section of Cardiology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: H
authors.initials: H
authors.lastname: Kubo
authors.forename: K B
authors.initials: KB
authors.lastname: Margulies
authors.forename: V
authors.initials: V
authors.lastname: Piacentino
authors.forename: J P
authors.initials: JP
authors.lastname: Gaughan
authors.forename: S R
authors.initials: SR
authors.lastname: Houser
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002478:Cells, Cultured; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism*; D006352:Heart Ventricles / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D011506:Proteins / Q000378:metabolism*; D012508:Sarcolemma / Q000737:chemistry; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D000099211:Phospholamban
chemical_list: D000319:Adrenergic beta-Antagonists; D002118:Calcium; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D011506:Proteins; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019831:Sodium-Calcium Exchanger; D000099211:Phospholamban