title: Exercise training improves the net balance of cardiac Ca2+ handling protein expression in heart failure.
abstract: The molecular basis of the beneficial effects associated with exercise training (ET) on overall ventricular function (VF) in heart failure (HF) remains unclear. We investigated potential Ca(2+) handling abnormalities and whether ET would improve VF of mice lacking alpha(2A)- and alpha(2C)-adrenoceptors (alpha(2A)/alpha(2C)ARKO) that have sympathetic hyperactivity-induced HF. A cohort of male wild-type (WT) and congenic alpha(2A)/alpha(2C)ARKO mice in a C57BL/J genetic background (5-7 mo of age) was randomly assigned into untrained and trained groups. VF was assessed by two-dimensional guided M-mode echocardiography. Cardiac myocyte width and ventricular fibrosis were evaluated with a computer-assisted morphometric system. Sarcoplasmic reticulum Ca(2+) ATPase (SERCA2), phospholamban (PLN), phospho-Ser(16)-PLN, phospho-Thr(17)-PLN, phosphatase 1 (PP1), and Na(+)-Ca(2+) exchanger (NCX) were analyzed by Western blotting. ET consisted of 8-wk running sessions of 60 min, 5 days/wk. alpha(2A)/alpha(2C)ARKO mice displayed exercise intolerance, systolic dysfunction, increased cardiac myocyte width, and ventricular fibrosis paralleled by decreased SERCA2 and increased NCX expression levels. ET in alpha(2A)/alpha(2C)ARKO mice improved exercise tolerance and systolic function. ET slightly reduced cardiac myocyte width, but unchanged ventricular fibrosis in alpha(2A)/alpha(2C)ARKO mice. ET significantly increased the expression of SERCA2 (20%) and phospho-Ser(16)-PLN (63%), phospho-Thr(17)-PLN (211%) in alpha(2A)/alpha(2C)ARKO mice. Furthermore, ET restored NCX and PP1 expression in alpha(2A)/alpha(2C)ARKO to untrained WT mice levels. Thus, we provide evidence that Ca(2+) handling is impaired in this HF model and that overall VF improved upon ET, which was associated to changes in the net balance of cardiac Ca(2+) handling proteins.
authors.affiliation: School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.
authors.forename: Natale P L
authors.initials: NP
authors.lastname: Rolim
authors.forename: Alessandra
authors.initials: A
authors.lastname: Medeiros
authors.forename: Kaleizu T
authors.initials: KT
authors.lastname: Rosa
authors.forename: Katt C
authors.initials: KC
authors.lastname: Mattos
authors.forename: Maria C
authors.initials: MC
authors.lastname: Irigoyen
authors.forename: Eduardo M
authors.initials: EM
authors.lastname: Krieger
authors.forename: Jose E
authors.initials: JE
authors.lastname: Krieger
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Negrão
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Brum
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D017079:Exercise Tolerance / Q000502:physiology; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D006339:Heart Rate / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics* / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium