Your browser doesn't support javascript.
loading
Accelerated onset of heart failure in mice during pressure overload with chronically decreased SERCA2 calcium pump activity.
Schultz, Jo El J; Glascock, Betty J; Witt, Sandra A; Nieman, Michelle L; Nattamai, Kalpana J; Liu, Lynne H; Lorenz, John N; Shull, Gary E; Kimball, Thomas R; Periasamy, Muthu.
Afiliação
  • Schultz Jel J; Dept. of Physiology and Cell Biology, The Ohio State Univ. College of Medicine, 304 Hamilton Hall, 1645 Neil Ave., Columbus, OH 43210, USA.
Am J Physiol Heart Circ Physiol ; 286(3): H1146-53, 2004 Mar.
Article em En | MEDLINE | ID: mdl-14630633
ABSTRACT
We recently developed a mouse model with a single functional allele of Serca2 (Serca2+/-) that shows impaired cardiac contractility and relaxation without overt heart disease. The goal of this study was to test the hypothesis that chronic reduction in sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)2 levels in combination with an increased hemodynamic load will result in an accelerated pathway to heart failure. Age-matched wild-type and Serca2+/- mice were subjected to 10 wk of pressure overload via transverse aortic coarctation surgery. Cardiac hypertrophy and heart failure were assessed by echocardiography, gravimetry/histology, hemodynamics, and Western blotting analyses. Our results showed that approximately 64% of coarcted Serca2+/- mice were in heart failure compared with 0% of coarcted wild-type mice (P < 0.05). Overall, morbidity and mortality were greatly increased in Serca2+/- mice under pressure overload. Echocardiography assessment revealed a significant increase in left ventricular (LV) mass, and LV hypertrophy in coarcted Serca2+/- mice converted from a concentric to an eccentric pattern, similar to that seen in human heart failure. Coarcted Serca2+/- mice had decreased contractile/systolic and relaxation/diastolic performance and/or function compared with coarcted wild-type mice (P < 0.05), despite a similar duration and degree of pressure overload. SERCA2a protein levels were significantly reduced (>50%) in coarcted Serca2+/- mice compared with noncoarcted and coarcted wild-type mice. Our findings suggest that reduction in SERCA2 levels in combination with an increased hemodynamic load results in an accelerated pathway to heart failure.
Assuntos
Buscar no Google
Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: ATPases Transportadoras de Cálcio / Insuficiência Cardíaca Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Am J Physiol Heart Circ Physiol Assunto da revista: CARDIOLOGIA / FISIOLOGIA Ano de publicação: 2004 Tipo de documento: Article País de afiliação: Estados Unidos
Buscar no Google
Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: ATPases Transportadoras de Cálcio / Insuficiência Cardíaca Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Am J Physiol Heart Circ Physiol Assunto da revista: CARDIOLOGIA / FISIOLOGIA Ano de publicação: 2004 Tipo de documento: Article País de afiliação: Estados Unidos