Relaxin Suppresses Atrial Fibrillation by Reversing Fibrosis and Myocyte Hypertrophy and Increasing Conduction Velocity and Sodium Current in Spontaneously Hypertensive Rat Hearts
| Autor: | Jamie Haney, Ashish Parikh, Randall L. Rasmusson, Glenna C.L. Bett, Charles F. McTiernan, Wenyu Xiang, David Schwartzman, Divyang Patel, Guy Salama, Aaron D. Kaplan, Sanjeev G. Shroff, Bo Lin, Lei Yang |
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| Rok vydání: | 2013 |
| Předmět: |
Male
medicine.medical_specialty Physiology Rats Inbred WKY Article Nerve conduction velocity Muscle hypertrophy Spontaneously hypertensive rat Heart Conduction System Fibrosis Rats Inbred SHR Internal medicine Atrial Fibrillation medicine Animals Humans Myocytes Cardiac Relaxin business.industry Atrial fibrillation Hypertrophy medicine.disease Recombinant Proteins Rats Endocrinology Cardiology Electrical conduction system of the heart Cardiomyopathies Cardiology and Cardiovascular Medicine business Hormone |
| Zdroj: | Circulation Research. 113:313-321 |
| ISSN: | 1524-4571 0009-7330 |
| Popis: | Rationale: Atrial fibrillation (AF) contributes significantly to morbidity and mortality in elderly and hypertensive patients and has been correlated to enhanced atrial fibrosis. Despite a lack of direct evidence that fibrosis causes AF, reversal of fibrosis is considered a plausible therapy. Objective: To evaluate the efficacy of the antifibrotic hormone relaxin (RLX) in suppressing AF in spontaneously hypertensive rats (SHR). Methods and Results: Normotensive Wistar-Kyoto (WKY) and SHR were treated for 2 weeks with vehicle (WKY+V and SHR+V) or RLX (0.4 mg/kg per day, SHR+RLX) using implantable mini-pumps. Hearts were perfused, mapped optically to analyze action potential durations, intracellular Ca 2+ transients, and restitution kinetics, and tested for AF vulnerability. SHR hearts had slower conduction velocity (CV; P P P P P + current density, I Na (≈2-fold in 48 hours) in human cardiomyocytes derived from inducible pluripotent stem cells (n=18/18; P Conclusions: RLX treatment suppressed AF in SHR hearts by increasing CV from a combination of reversal of fibrosis and hypertrophy and by increasing I Na . The study provides compelling evidence that RLX may provide a novel therapy to manage AF in humans by reversing fibrosis and hypertrophy and by modulating cardiac ionic currents. |
| Databáze: | OpenAIRE |
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