title: Exercise training normalizes altered calcium-handling proteins during development of heart failure.
abstract: The cardiac sarcoplasmic reticulum calcium-ATPase (SERCA2a), Na+/Ca2+ exchanger (NCX1), and ryanodine receptor (RyR2) are proteins involved in the regulation of myocyte calcium. We tested whether exercise training (ET) alters those proteins during development of chronic heart failure (CHF). Ten dogs were chronically instrumented to permit hemodynamic measurements. Five dogs underwent 4 wk of cardiac pacing (210 beats/min for 3 wk and 240 beats/min for the 4th wk), whereas five dogs underwent the same pacing regimen plus daily ET (5.1 +/- 0.3 km/h, 2 h/day). Paced animals developed CHF characterized by hemodynamic abnormalities and reduced ejection fraction. ET preserved resting hemodynamics and ejection fraction. Left ventricular samples were obtained from all dogs and another five normal dogs for mRNA (Northern analysis, band intensities normalized to glyceraldehyde-3-phosphate dehydrogenase) and protein level (Western analysis, band intensities normalized to tubulin) measurements. In failing hearts, SERCA2a was decreased by 33% (P < 0.05) and 65% (P < 0.05) in mRNA and protein level, respectively, compared with normal hearts; there was only an 8.6% reduction in mRNA and a 32% reduction in protein in exercised animals (P < 0.05 from CHF). mRNA expression of NCX1 increased by 44% in paced-only dogs compared with normal (P < 0.05) but only by 22% in trained dogs (P < 0.05 vs. CHF); protein level of NCX1 was elevated in paced-only dogs (71%, P < 0.05) but partially normalized by ET (33%, P < 0.05 from CHF). RyR2 was not altered in any of the dogs. In conclusion, long-term ET may ameliorate cardiac deterioration during development of CHF, in part via normalization of myocardial calcium-handling proteins.
authors.affiliation: Division of Circulatory Physiology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York City, NY 10032, USA.
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.forename: Dan Feng
authors.initials: DF
authors.lastname: Mei
authors.forename: An-Guo
authors.initials: AG
authors.lastname: Gu
authors.forename: Su
authors.initials: S
authors.lastname: Wang
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lentzner
authors.forename: David E
authors.initials: DE
authors.lastname: Gutstein
authors.forename: Donna
authors.initials: D
authors.lastname: Zwas
authors.forename: Shunichi
authors.initials: S
authors.lastname: Homma
authors.forename: Geng-Hua
authors.initials: GH
authors.lastname: Yi
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D004285:Dogs; D004452:Echocardiography; D015870:Gene Expression / Q000502:physiology; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology; D010138:Pacemaker, Artificial; D010805:Physical Conditioning, Animal / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism; D017725:Ventricular Pressure / Q000502:physiology; D014851:Wakefulness
chemical_list: D012333:RNA, Messenger; D019837:Ryanodine Receptor Calcium Release Channel; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium