Corin overexpression improves cardiac function, heart failure, and survival in mice with dilated cardiomyopathy

Inna P. Gladysheva, Dong Wang, Rachel A. McNamee, Aiilyan K. Houng, Almois A. Mohamad, T. Michael Fan, Guy L. Reed

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)327-332
Number of pages6
JournalHypertension
Volume61
Issue number2
DOIs
StatePublished - Feb 1 2013

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Keywords

  • corin
  • dilated cardiomyopathy
  • heart failure
  • natriuretic peptides

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Gladysheva, I. P., Wang, D., McNamee, R. A., Houng, A. K., Mohamad, A. A., Fan, T. M., & Reed, G. L. (2013). Corin overexpression improves cardiac function, heart failure, and survival in mice with dilated cardiomyopathy. Hypertension, 61(2), 327-332. https://doi.org/10.1161/HYPERTENSIONAHA.112.193631