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This Article Full Text Full Text (PDF) All Versions of this Article: 296/6/H1804    most recent 01033.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Yasuno, S. Articles by Nakao, K. PubMed PubMed Citation Articles by Yasuno, S. Articles by Nakao, K.

Endogenous cardiac natriuretic peptides protect the heart in a mouse model of dilated cardiomyopathy and sudden death

¹Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto; ²Department of Biophysics, National Cardiovascular Center Research Institute, Suita; and ³EBM Research Center, Kyoto University Graduate School of Medicine, Kyoto, Japan

Submitted 26 September 2008 ; accepted in final form 1 April 2009

Ventricular myocytes are known to show increased expression of the cardiac hormones atrial and brain natriuretic peptide (ANP and BNP, respectively) in response to pathological stress on the heart, but their function during the progression of nonischemic dilated cardiomyopathy remains unclear. In this study, we crossed a mouse model of dilated cardiomyopathy and sudden death, which we generated by cardioselectively overexpressing a dominant-negative form of the transcriptional repressor neuron-restrictive silencer factor (dnNRSF Tg mice), with mice lacking guanylyl cyclase-A (GC-A), a common receptor for ANP and BNP, to assess the effects of endogenously expressed natriuretic peptides during progression of the cardiomyopathy seen in dnNRSF Tg mice. We found that dnNRSF Tg;GC-A^–/– mice were born normally, but then most died within 4 wk. The survival rates among dnNRSF Tg;GC-A^+/– and dnNRSF Tg mice were comparable, but dnNRSF Tg;GC-A^+/– mice showed greater systolic dysfunction and a more severe cardiomyopathic phenotype than dnNRSF Tg mice. Collectively, our findings suggest that endogenous ANP/BNP protects the heart against the death and progression of pathological remodeling in a mouse model of dilated cardiomyopathy and sudden death.

neuron-restrictive silencer factor; guanylyl cyclase-A; cardiomyopathy; sudden death