Impaired sinoatrial node function and increased susceptibility to atrial fibrillation in mice lacking natriuretic peptide receptor C
| Autor: | Gibanananda Ray, Hailey J. Jansen, Martin Mackasey, Motahareh Moghtadaei, Sara A. Rafferty, Iuliia Polina, Oleg Bogachev, Emmanuel E. Egom, Kimberly Vella, Rhea Hurnik, Rui Hua, Robert A. Rose |
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| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Atrial action potential Heart disease Physiology Action Potentials 030204 cardiovascular system & hematology Cardiovascular Mice 03 medical and health sciences 0302 clinical medicine Fibrosis Internal medicine Atrial Fibrillation medicine Animals Myocytes Cardiac cardiovascular diseases Receptor Cells Cultured Sinoatrial Node 030304 developmental biology 0303 health sciences Sinoatrial node Cardiac electrophysiology business.industry Atrial fibrillation medicine.disease 3. Good health Cardiovascular physiology Mice Inbred C57BL medicine.anatomical_structure Endocrinology cardiovascular system Collagen business Receptors Atrial Natriuretic Factor |
| Zdroj: | The Journal of Physiology. 593:1127-1146 |
| ISSN: | 1469-7793 0022-3751 |
| DOI: | 10.1113/jphysiol.2014.283135 |
| Popis: | Natriuretic peptides (NPs) are critical regulators of the cardiovascular system that are currently viewed as possible therapeutic targets for the treatment of heart disease. Recent work demonstrates potent NP effects on cardiac electrophysiology, including in the sinoatrial node (SAN) and atria. NPs elicit their effects via three NP receptors (NPR-A, NPR-B and NPR-C). Among these receptors, NPR-C is poorly understood. Accordingly, the goal of this study was to determine the effects of NPR-C ablation on cardiac structure and arrhythmogenesis. Cardiac structure and function were assessed in wild-type (NPR-C(+/+)) and NPR-C knockout (NPR-C(-/-)) mice using echocardiography, intracardiac programmed stimulation, patch clamping, high-resolution optical mapping, quantitative polymerase chain reaction and histology. These studies demonstrate that NPR-C(-/-) mice display SAN dysfunction, as indicated by a prolongation (30%) of corrected SAN recovery time, as well as an increased susceptibility to atrial fibrillation (6% in NPR-C(+/+) vs. 47% in NPR-C(-/-)). There were no differences in SAN or atrial action potential morphology in NPR-C(-/-) mice; however, increased atrial arrhythmogenesis in NPR-C(-/-) mice was associated with reductions in SAN (20%) and atrial (15%) conduction velocity, as well as increases in expression and deposition of collagen in the atrial myocardium. No differences were seen in ventricular arrhythmogenesis or fibrosis in NPR-C(-/-) mice. This study demonstrates that loss of NPR-C results in SAN dysfunction and increased susceptibility to atrial arrhythmias in association with structural remodelling and fibrosis in the atrial myocardium. These findings indicate a critical protective role for NPR-C in the heart. |
| Databáze: | OpenAIRE |
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