| First Author | Schultz Jel J | Year | 2004 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 286 |
| Issue | 3 | Pages | H1146-53 |
| PubMed ID | 14630633 | Mgi Jnum | J:95608 |
| Mgi Id | MGI:3526623 | Doi | 10.1152/ajpheart.00720.2003 |
| Citation | Schultz Jel J, et al. (2004) Accelerated onset of heart failure in mice during pressure overload with chronically decreased SERCA2 calcium pump activity. Am J Physiol Heart Circ Physiol 286(3):H1146-53 |
| abstractText | 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. |
