Patients with end-stage congestive heart failure treated with β-adrenergic receptor antagonists have improved ventricular myocyte calcium regulatory protein abundance

• Published in: Circulation (New York, N.Y.) N.Y.), 2001-08, Vol.104 (9), p.1012-1018
• Main Authors: KUBO, Hajime, MARGULIES, Kenneth B, PIACENTINO, Valentino III, GAUGHAN, John P, HOUSER, Steven R
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Antagonists - therapeutic use; Biological and medical sciences; Blotting, Western; Calcium - metabolism; Calcium-Binding Proteins - metabolism; Calcium-Transporting ATPases - metabolism; Cardiovascular system; Cells, Cultured; Heart Failure - drug therapy; Heart Failure - metabolism; Heart Ventricles - cytology; Heart Ventricles - metabolism; Humans; Medical sciences; Middle Aged; Pharmacology. Drug treatments; Proteins - metabolism; Sarcolemma - chemistry; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Sodium-Calcium Exchanger - metabolism; Vasodilator agents. Cerebral vasodilators
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/hc3401.095073

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. 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. betaB treatment in CHF patients can normalize the abundance of myocyte Ca(2+) regulatory proteins and improve Ca(2+)-handling.