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

Abstract

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.

• Authors: Shinji Yasuno, Satoru Usami, Koichiro Kuwahara, Michio Nakanishi, Yuji Arai, Hideyuki Kinoshita, Yasuaki Nakagawa, Masataka Fujiwara, Masao Murakami, Kenji Ueshima, Masaki Harada, Kazuwa Nakao
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 296 Issue 6 Pg. H1804-10 (Jun 2009) ISSN: 0363-6135 [Print] United States
• PMID: 19346456 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RE1-silencing transcription factor
• RNA, Messenger
• Repressor Proteins
• Natriuretic Peptide, Brain
• Atrial Natriuretic Factor
• Receptors, Atrial Natriuretic Factor
• atrial natriuretic factor receptor A

Topics

• Animals
• Atrial Natriuretic Factor (genetics, metabolism)
• Cardiomyopathy, Dilated (mortality, pathology, physiopathology)
• Death, Sudden, Cardiac (prevention & control)
• Disease Models, Animal
• Female
• Gene Expression (physiology)
• Kaplan-Meier Estimate
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Myocardium (metabolism, pathology)
• Natriuretic Peptide, Brain (genetics, metabolism)
• Phenotype
• RNA, Messenger (metabolism)
• Receptors, Atrial Natriuretic Factor (genetics)
• Repressor Proteins (genetics)
• Systole
• Ventricular Remodeling (physiology)