Cardiac contractility modulation electrical signals normalize activity, expression, and phosphorylation of the Na+-Ca2+ exchanger in heart failure.
BACKGROUND
Expression and phosphorylation of the cardiac Na(+)-Ca(2+) exchanger-1 (NCX-1) are up-regulated in heart failure (HF). We examined the effects of chronic cardiac contractility modulation (CCM) therapy on the expression and phosphorylation of NCX-1 and its regulators GATA-4 and FOG-2 in HF dogs.


RESULTS
Studies were performed in LV tissue from 7 CCM-treated HF dogs, 7 untreated HF dogs, and 6 normal (NL) dogs. mRNA expression of NCX-1, GATA-4, and FOG-2 was measured using reverse transcriptase polymerase chain reaction, and protein level was determined by Western blotting. Phosphorylated NCX-1 (P-NCX) was determined using a phosphoprotein enrichment kit. Compared with NL dogs, NCX-1 mRNA and protein expression and GATA-4 mRNA and protein expression increased in untreated HF dogs, whereas FOG-2 expression decreased. Compared with NL dogs, the level of P-NCX-1 normalized to total NCX-1 increased in untreated HF dogs (0.80+/-0.10 vs 0.37+/-0.04; P < .05). CCM therapy normalized NCX-1 expression, GATA-4, and FOG-2 expression, and the ratio of P-NCX-1 to total NCX-1 (0.62+/-0.10).


CONCLUSIONS
Chronic monotherapy with CCM restores expression and phosphorylation of NCX-1. These findings are consistent with previous observations of improved LV function and normalized sarcoplasmic reticulum calcium cycling in the left ventricles of HF dogs treated with CCM therapy.
Gupta
Ramesh C
RC
Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Heart and Vascular Institute, Detroit, Michigan 48202, USA.
Mishra
Sudhish
S
Wang
Mengjun
M
Jiang
Alice
A
Rastogi
Sharad
S
Rousso
Benny
B
Mika
Yuval
Y
Sabbah
Hani N
HN
D000704:Analysis of Variance; D000818:Animals; D002304:Cardiac Pacing, Artificial / Q000379:methods*; D004285:Dogs; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006333:Heart Failure / Q000503:physiopathology / Q000628:therapy*; D009200:Myocardial Contraction / Q000502:physiology*; D010138:Pacemaker, Artificial; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism; D015398:Signal Transduction; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000502:physiology
D050991:GATA4 Transcription Factor; D012333:RNA, Messenger; D019831:Sodium-Calcium Exchanger; D014157:Transcription Factors