| First Author | Minamisawa S | Year | 1999 |
| Journal | Cell | Volume | 99 |
| Issue | 3 | Pages | 313-22 |
| PubMed ID | 10555147 | Mgi Jnum | J:58299 |
| Mgi Id | MGI:1347184 | Doi | 10.1016/s0092-8674(00)81662-1 |
| Citation | Minamisawa S, et al. (1999) Chronic phospholamban-sarcoplasmic reticulum calcium ATPase interaction is the critical calcium cycling defect in dilated cardiomyopathy. Cell 99(3):313-22 |
| abstractText | Dilated cardiomyopathy and end-stage heart failure result in multiple defects in cardiac excitation-contraction coupling. Via complementation of a genetically based mouse model of dilated cardiomyopathy, we now provide evidence that progressive chamber dilation and heart failure are dependent on a Ca2+ cycling defect in the cardiac sarcoplasmic reticulum. The ablation of a muscle-specific sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) inhibitor, phospholamban, rescued the spectrum of phenotypes that resemble human heart failure. Inhibition of phospholamban-SERCA2a interaction via in vivo expression of a phospholamban point mutant dominantly activated the contractility of ventricular muscle cells. Thus, interfering with phospholamban-SERCA2a interaction may provide a novel therapeutic approach for preventing the progression of dilated cardiomyopathy. |
