[HTML][HTML] Chronic phospholamban–sarcoplasmic reticulum calcium ATPase interaction is the critical calcium cycling defect in dilated cardiomyopathy

S Minamisawa, M Hoshijima, G Chu, CA Ward, K Frank… - Cell, 1999 - cell.com
S Minamisawa, M Hoshijima, G Chu, CA Ward, K Frank, Y Gu, ME Martone, Y Wang, J Ross…
Cell, 1999cell.com
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 Ca 2+ cycling defect in the cardiac sarcoplasmic reticulum.
The ablation of a muscle-specific sarcoplasmic reticulum Ca 2+ ATPase (SERCA2a)
inhibitor, phospholamban, rescued the spectrum of phenotypes that resemble human heart …
Abstract
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.
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