CBS 2019
CBSMD教育中心
中 文

Scientific Library

Abstract

Recommended Article

Stretch-induced sarcoplasmic reticulum calcium leak is causatively associated with atrial fibrillation in pressure-overloaded hearts Sustainable Antirestenosis Effect With a Low-Dose Drug-Coated Balloon: The ILLUMENATE European Randomized Clinical Trial 2-Year Results Procedural and Short-Term Results With the New Watchman FLX Left Atrial Appendage Occlusion Device Abnormalities in 3-Dimensional Left Ventricular Mechanics With Anthracycline Chemotherapy Are Associated With Systolic and Diastolic Dysfunction Cardio-Oncology Services: rationale, organization, and implementation: A report from the ESC Cardio-Oncology council Outcomes with drug-coated balloons in small-vessel coronary artery disease Association of Effective Regurgitation Orifice Area to Left Ventricular End-Diastolic Volume Ratio With Transcatheter Mitral Valve Repair OutcomesA Secondary Analysis of the COAPT Trial Current Status and Future Prospects of Transcatheter Mitral Valve Replacement: JACC State-of-the-Art Review

Original ResearchVolume 117, Issue 4, 1 April 2021, Pages 1091–1102

JOURNAL:Cardiovasc Res. Article Link

Stretch-induced sarcoplasmic reticulum calcium leak is causatively associated with atrial fibrillation in pressure-overloaded hearts

Y Zhang, Y Qi, JJ Li, WJ He et al. Keywords: AF; hypertension; underlying mechanism

ABSTRACT

AIMS - Despite numerous reports documenting an important role of hypertension in the development of atrial fibrillation (AF), the detailed mechanism underlying the pathological process remains incompletely understood. Here, we aim to test the hypothesis that diastolic sarcoplasmic reticulum (SR) Ca2+leak in atrial myocytes, induced by mechanical stretch due to elevated pressure in the left atrium (LA), plays an essential role in the AF development in pressure-overloaded hearts.


METHODS AND RESULTS - Isolated mouse atrial myocytes subjected to acute axial stretch displayed an immediate elevation of SR Ca2+leak. Using a mouse model of transverse aortic constriction (TAC), the relation between stretch, SR Ca2+leak, and AF susceptibility was further tested. At 36 h post-TAC, SR Ca2+leak in cardiomyocytes from the LA (with haemodynamic stress), but not right atrium (without haemodynamic stress), significantly increased, which was further elevated at 4 weeks post-TAC. Accordingly, AF susceptibility to atrial burst pacing in the 4-week TAC mice were also significantly increased, which was unaffected by inhibition of atrial fibrosis or inflammation via deletion of galectin-3. Western blotting revealed that type 2 ryanodine receptor (RyR2) in left atrial myocytes of TAC mice was oxidized due to activation and up-regulation of Nox2 and Nox4. Direct rescue of dysfunctional RyR2 with dantrolene or rycal S107 reduced diastolic SR Ca2+leak in left atrial myocytes and prevented atrial burst pacing stimulated AF.


CONCLUSIONS -Our study demonstrated for the first time the increased SR Ca2+leak mediated by enhanced oxidative stress in left atrial myocytes that is causatively associated with higher AF susceptibility in pressure-overloaded hearts.