TY - JOUR
T1 - Corin overexpression improves cardiac function, heart failure, and survival in mice with dilated cardiomyopathy
AU - Gladysheva, Inna P.
AU - Wang, Dong
AU - McNamee, Rachel A.
AU - Houng, Aiilyan K.
AU - Mohamad, Almois A.
AU - Fan, T. Michael
AU - Reed, Guy L.
PY - 2013/2
Y1 - 2013/2
N2 - Heart failure, caused by dilated cardiomyopathy and other cardiac disorders such as hypertension, is a major public health problem with high morbidity and mortality. Corin, a cardiac enzyme that cleaves natriuretic peptides, is a promising biomarker of cardiomyopathy and heart failure, but its functional role in these processes is not understood. We evaluated the potential effects of corin in mice with a well-characterized model of dilated cardiomyopathy. Mice with dilated cardiomyopathy developed heart failure, reduced contractile function, cardiac fibrosis, and accelerated mortality in the setting of low corin expression. In wild-type mice, transgenic, cardiac-targeted, overexpression of corin enhanced cyclic guanosine monophosphate and blood pressure responses to pro-atrial natriuretic peptide, but did not affect heart size, contractility, body weights, survival, and blood pressure. In mice with dilated cardiomyopathy, corin overexpression significantly reduced the development of myocardial fibrosis (P<0.05). Corin overexpression also enhanced heart contractile function (fractional shortening and ejection fraction; P<0.01) and it significantly reduced heart failure as assessed by lung water (P<0.05) and alveolar congestion (P<0.001). Consistent with these observations, corin overexpression significantly prolonged life in mice with dilated cardiomyopathy (P<0.0001). These results provide the first experimental evidence that corin expression plays a role in cardiomyopathy by modulating myocardial fibrosis, cardiac function, heart failure, and survival.
AB - Heart failure, caused by dilated cardiomyopathy and other cardiac disorders such as hypertension, is a major public health problem with high morbidity and mortality. Corin, a cardiac enzyme that cleaves natriuretic peptides, is a promising biomarker of cardiomyopathy and heart failure, but its functional role in these processes is not understood. We evaluated the potential effects of corin in mice with a well-characterized model of dilated cardiomyopathy. Mice with dilated cardiomyopathy developed heart failure, reduced contractile function, cardiac fibrosis, and accelerated mortality in the setting of low corin expression. In wild-type mice, transgenic, cardiac-targeted, overexpression of corin enhanced cyclic guanosine monophosphate and blood pressure responses to pro-atrial natriuretic peptide, but did not affect heart size, contractility, body weights, survival, and blood pressure. In mice with dilated cardiomyopathy, corin overexpression significantly reduced the development of myocardial fibrosis (P<0.05). Corin overexpression also enhanced heart contractile function (fractional shortening and ejection fraction; P<0.01) and it significantly reduced heart failure as assessed by lung water (P<0.05) and alveolar congestion (P<0.001). Consistent with these observations, corin overexpression significantly prolonged life in mice with dilated cardiomyopathy (P<0.0001). These results provide the first experimental evidence that corin expression plays a role in cardiomyopathy by modulating myocardial fibrosis, cardiac function, heart failure, and survival.
KW - corin
KW - dilated cardiomyopathy
KW - heart failure
KW - natriuretic peptides
UR - http://www.scopus.com/inward/record.url?scp=84873058628&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84873058628&partnerID=8YFLogxK
U2 - 10.1161/HYPERTENSIONAHA.112.193631
DO - 10.1161/HYPERTENSIONAHA.112.193631
M3 - Article
C2 - 23232642
AN - SCOPUS:84873058628
SN - 0194-911X
VL - 61
SP - 327
EP - 332
JO - Hypertension
JF - Hypertension
IS - 2
ER -