Author + information
- Received March 30, 2018
- Revision received August 15, 2018
- Accepted August 16, 2018
- Published online December 31, 2018.
- Martin Mackasey, BSca,b,∗,
- Emmanuel E. Egom, MD, PhDb,∗,
- Hailey J. Jansen, PhDa,b,∗,
- Rui Hua, PhDb,
- Motahareh Moghtadaei, PhDb,
- Yingjie Liu, PhDa,
- Jaspreet Kaur, PhDa,
- Megan D. McRae, BHSca,
- Oleg Bogachev, MDb,
- Sara A. Rafferty, MScb,
- Gibanananda Ray, PhDb,
- Adam W. Kirkby, MSca and
- Robert A. Rose, PhDa,b,∗ ()
- aDepartment of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada, and Department of Physiology and Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- bDepartment of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
- ↵∗Address for correspondence:
Prof. Robert Alan Rose, Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, GAC66, Health Research Innovation Centre, 3280 Hospital Drive NW, Calgary, Alberta T2N 4Z6, Canada.
• SAN disease is prevalent in hypertension and heart failure and can be induced by chronic Ang II treatment in mice.
• Ang II caused SAN disease in mice in association with impaired electrical conduction, reduction in the hyperpolarization-activated current (If) in SAN myocytes, and increased SAN fibrosis.
• Ang II-induced SAN disease was worsened in mice lacking NPR-C in association with enhanced SAN fibrosis.
• Mice co-treated with Ang II and an NPR-C agonist (cANF) were protected from SAN disease.
• NPR-C may represent a new target to protect against Ang II-induced SAN disease.
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.
↵∗ Mr. Mackasey, Dr. Egom, and Dr. Jansen contributed equally to this work and are joint first authors.
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.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received March 30, 2018.
- Revision received August 15, 2018.
- Accepted August 16, 2018.
- 2018 The Authors