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Reply to ‘Re-evaluating sarcoplasmic reticulum function in heart failure’

Nature Medicine volume 6, pages 942–943 (2000)Cite this article

Chien replies

Several complex signaling pathways can lead to dilated cardiomyopathy and heart failure (for review, see refs. 7,8). As noted in the letter, the ablation of phospholamban can completely arrest the progression of heart failure in a gene targeted mouse model of dilated cardiomyopathy3, based on a deficiency in the muscle specific cytoskeletal protein, MLP. This model displays many conserved features of the human disease, and provided the first evidence that dilated cardiomyopathies might arise from mutations in Z disk components, a finding confirmed in human studies (for review, see ref. 9). However, cardiomyopathy is a heterogeneous disorder with diverse etiologies. Molkentin and colleagues appropriately argue for caution, noting that defects in calcium cycling might not represent a universal pathway for dilated cardiomyopathy. Their results clearly indicate that phospholamban gene ablation cannot rescue the dilated cardiomyopathy that accompanies tropomodulin over-expression, using several independent endpoints, including survival.

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  1. University of California, San Diego-Salk Program in Molecular Medicine, Institute of Molecular Medicine, La Jolla, 92093, California

    Kenneth R. Chien

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Chien, K. Reply to ‘Re-evaluating sarcoplasmic reticulum function in heart failure’. Nat Med 6, 942–943 (2000). https://doi.org/10.1038/79595

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