Natriuretic Peptide Receptor-C Protects Against Angiotensin II-Mediated Sinoatrial Node Disease in Mice

Martin Mackasey; Emmanuel E. Egom; Hailey J. Jansen; Rui Hua; Motahareh Moghtadaei; Yingjie Liu; Jaspreet Kaur; Megan D. McRae; Oleg Bogachev; Sara A. Rafferty; Gibanananda Ray; Adam W. Kirkby; Robert A. Rose

doi:10.1016/j.jacbts.2018.08.004

Natriuretic Peptide Receptor-C Protects Against Angiotensin II-Mediated Sinoatrial Node Disease in Mice

Martin Mackasey, Emmanuel E. Egom, Hailey J. Jansen, Rui Hua, Motahareh Moghtadaei, Yingjie Liu, Jaspreet Kaur, Megan D. McRae, Oleg Bogachev, Sara A. Rafferty, Gibanananda Ray, Adam W. Kirkby, Robert A. Rose

Medicine

Research output: Contribution to journal › Article › peer-review

30 Citations (Scopus)

Abstract

Sinoatrial node (SAN) disease mechanisms are poorly understood, and therapeutic options are limited. Natriuretic peptide(s) (NP) are cardioprotective hormones whose effects can be mediated partly by the NP receptor C (NPR-C). We investigated the role of NPR-C in angiotensin II (Ang II)-mediated SAN disease in mice. Ang II caused SAN disease due to impaired electrical activity in SAN myocytes and increased SAN fibrosis. Strikingly, Ang II treatment in NPR-C ^−/− mice worsened SAN disease, whereas co-treatment of wild-type mice with Ang II and a selective NPR-C agonist (cANF) prevented SAN dysfunction. NPR-C may represent a new target to protect against the development of Ang II-induced SAN disease.

Original language	English
Pages (from-to)	824-843
Number of pages	20
Journal	JACC: Basic to Translational Science
Volume	3
Issue number	6
DOIs	https://doi.org/10.1016/j.jacbts.2018.08.004
Publication status	Published - Dec 2018

Bibliographical note

Funding Information:
Supported by Canadian Institutes of Health Research grants MOP 93718 and 142486 to Prof. Rose. Prof. Rose holds a New Investigator Award from the Heart and Stroke Foundation of Canada. Dr. Egom is an employee of ECTRS Ltd. Mr. Mackasey is the recipient of a Libin Cardiovascular Institute of Alberta graduate scholarship. Dr. Egom held a Heart and Stroke Foundation of Canada fellowship. Dr. Jansen holds a Killam postdoctoral fellowship. Dr. Liu is the recipient of a Cumming School of Medicine postdoctoral scholarship. The other authors have reported that they have no industry relationships relevant to the contents of this paper to disclose. Dr. Egom is currently affiliated with the Department of Medicine, St. Martha’s Regional Hospital, Antigonish, Nova Scotia, Canada.

Publisher Copyright:
© 2018 The Authors

ASJC Scopus Subject Areas

Cardiology and Cardiovascular Medicine

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10.1016/j.jacbts.2018.08.004

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Mackasey, M., Egom, E. E., Jansen, H. J., Hua, R., Moghtadaei, M., Liu, Y., Kaur, J., McRae, M. D., Bogachev, O., Rafferty, S. A., Ray, G., Kirkby, A. W., & Rose, R. A. (2018). Natriuretic Peptide Receptor-C Protects Against Angiotensin II-Mediated Sinoatrial Node Disease in Mice. JACC: Basic to Translational Science, 3(6), 824-843. https://doi.org/10.1016/j.jacbts.2018.08.004

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title = "Natriuretic Peptide Receptor-C Protects Against Angiotensin II-Mediated Sinoatrial Node Disease in Mice",

abstract = " Sinoatrial node (SAN) disease mechanisms are poorly understood, and therapeutic options are limited. Natriuretic peptide(s) (NP) are cardioprotective hormones whose effects can be mediated partly by the NP receptor C (NPR-C). We investigated the role of NPR-C in angiotensin II (Ang II)-mediated SAN disease in mice. Ang II caused SAN disease due to impaired electrical activity in SAN myocytes and increased SAN fibrosis. Strikingly, Ang II treatment in NPR-C −/− mice worsened SAN disease, whereas co-treatment of wild-type mice with Ang II and a selective NPR-C agonist (cANF) prevented SAN dysfunction. NPR-C may represent a new target to protect against the development of Ang II-induced SAN disease. ",

author = "Martin Mackasey and Egom, {Emmanuel E.} and Jansen, {Hailey J.} and Rui Hua and Motahareh Moghtadaei and Yingjie Liu and Jaspreet Kaur and McRae, {Megan D.} and Oleg Bogachev and Rafferty, {Sara A.} and Gibanananda Ray and Kirkby, {Adam W.} and Rose, {Robert A.}",

note = "Funding Information: Supported by Canadian Institutes of Health Research grants MOP 93718 and 142486 to Prof. Rose. Prof. Rose holds a New Investigator Award from the Heart and Stroke Foundation of Canada. Dr. Egom is an employee of ECTRS Ltd. Mr. Mackasey is the recipient of a Libin Cardiovascular Institute of Alberta graduate scholarship. Dr. Egom held a Heart and Stroke Foundation of Canada fellowship. Dr. Jansen holds a Killam postdoctoral fellowship. Dr. Liu is the recipient of a Cumming School of Medicine postdoctoral scholarship. The other authors have reported that they have no industry relationships relevant to the contents of this paper to disclose. Dr. Egom is currently affiliated with the Department of Medicine, St. Martha{\textquoteright}s Regional Hospital, Antigonish, Nova Scotia, Canada. Publisher Copyright: {\textcopyright} 2018 The Authors",

year = "2018",

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doi = "10.1016/j.jacbts.2018.08.004",

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AU - Hua, Rui

AU - Moghtadaei, Motahareh

AU - Liu, Yingjie

AU - Kaur, Jaspreet

AU - McRae, Megan D.

AU - Bogachev, Oleg

AU - Rafferty, Sara A.

AU - Ray, Gibanananda

AU - Kirkby, Adam W.

AU - Rose, Robert A.

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N2 - Sinoatrial node (SAN) disease mechanisms are poorly understood, and therapeutic options are limited. Natriuretic peptide(s) (NP) are cardioprotective hormones whose effects can be mediated partly by the NP receptor C (NPR-C). We investigated the role of NPR-C in angiotensin II (Ang II)-mediated SAN disease in mice. Ang II caused SAN disease due to impaired electrical activity in SAN myocytes and increased SAN fibrosis. Strikingly, Ang II treatment in NPR-C −/− mice worsened SAN disease, whereas co-treatment of wild-type mice with Ang II and a selective NPR-C agonist (cANF) prevented SAN dysfunction. NPR-C may represent a new target to protect against the development of Ang II-induced SAN disease.

AB - Sinoatrial node (SAN) disease mechanisms are poorly understood, and therapeutic options are limited. Natriuretic peptide(s) (NP) are cardioprotective hormones whose effects can be mediated partly by the NP receptor C (NPR-C). We investigated the role of NPR-C in angiotensin II (Ang II)-mediated SAN disease in mice. Ang II caused SAN disease due to impaired electrical activity in SAN myocytes and increased SAN fibrosis. Strikingly, Ang II treatment in NPR-C −/− mice worsened SAN disease, whereas co-treatment of wild-type mice with Ang II and a selective NPR-C agonist (cANF) prevented SAN dysfunction. NPR-C may represent a new target to protect against the development of Ang II-induced SAN disease.

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Natriuretic Peptide Receptor-C Protects Against Angiotensin II-Mediated Sinoatrial Node Disease in Mice

Abstract

Bibliographical note

ASJC Scopus Subject Areas

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