Exercise training improves the net balance of cardiac Ca2+ handling protein expression in heart failure

Autor(es)

Rolim, Natale P. L. ; Medeiros, Alessandra ; Rosa, Kaleizu T. ; Mattos, Katt C. ; Irigoyen, Maria C. ; Krieger, Eduardo M. ; Krieger, Jose E. ; Negrão, Carlos E. ^[8] ; Brum, Patricia C.

• Tipo de documento: Artigo Científico
• Fonte: Physiological Genomics; v. 29, n. 3, p. 246-252, May 2007.
• Área do conhecimento: Ciências da Saúde - Medicina
• Assunto(s): Condicionamento físico Insuficiência cardíaca Hemodinâmica Expressão gênica ATPases transportadoras de cálcio do retículo sarcoplasmático Trifosfato de adenosina Cálcio

Resumo

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 Ca2+ handling abnormalities and whether ET would improve VF of mice lacking 2A- and 2C-adrenoceptors (2A/2CARKO) that have sympathetic hyperactivity-induced HF. A cohort of male wild-type (WT) and congenic 2A/2CARKO 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 Ca2+ ATPase (SERCA2), phospholamban (PLN), phospho-Ser16-PLN, phospho-Thr17-PLN, phosphatase 1 (PP1), and Na+-Ca2+ exchanger (NCX) were analyzed by Western blotting. ET consisted of 8-wk running sessions of 60 min, 5 days/wk. 2A/2CARKO mice displayed exercise intolerance, systolic dysfunction, increased cardiac myocyte width, and ventricular fibrosis paralleled by decreased SERCA2 and increased NCX expression levels. ET in 2A/2CARKO mice improved exercise tolerance and systolic function. ET slightly reduced cardiac myocyte width, but unchanged ventricular fibrosis in 2A/2CARKO mice. ET significantly increased the expression of SERCA2 (20%) and phospho-Ser16-PLN (63%), phospho-Thr17-PLN (211%) in 2A/2CARKO mice. Furthermore, ET restored NCX and PP1 expression in 2A/2CARKO to untrained WT mice levels. Thus, we provide evidence that Ca2+ 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 Ca2+ handling proteins. (AU)

• Processo FAPESP: 02/04588-8 - Efeito do treinamento físico na cardiomiopatia induzida por hiperatividade simpática em camundongos knockout para os receptores alfa 2a e alfa 2a e alfa 2c adrenérgicos
• Beneficiário: Patricia Chakur Brum
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 04/00745-7 - Efeito do treinamento físico na cardiomiopatia induzida por hiperatividade simpática em camundongos nocaute para os receptores alfa 2A/alfa 2C-adrenérgicos
• Beneficiário: Alessandra Medeiros
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto