Chronic phospholamban-sarcoplasmic reticulum calcium ATPase interaction is the critical calcium cycling defect in dilated cardiomyopathy.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Minamisawa, S; Hoshijima, M; Chu, G; Ward, CA; Frank, K; Gu, Y; Martone, ME; Wang, Y; Ross, J; Kranias, EG; Giles, WR; Chien, KR

Published Date

  • October 29, 1999

Published In

Volume / Issue

  • 99 / 3

Start / End Page

  • 313 - 322

PubMed ID

  • 10555147

International Standard Serial Number (ISSN)

  • 0092-8674

Digital Object Identifier (DOI)

  • 10.1016/s0092-8674(00)81662-1


  • eng

Conference Location

  • United States