Key result
Metoprolol attenuated epicardial adipose tissue infiltration and alleviated its profibrotic effect on the atrial myocardium by inhibiting adipokine secretion in a canine model of chronic OSA.
Why the study?
Whether chronic obstructive sleep apnea promotes epicardial adipose tissue secretion of profibrotic adipokines contributing to atrial fibrosis, and the potential therapeutic effects of metoprolol, remain unknown.
Does metoprolol reduce profibrotic remodeling of epicardial adipose tissue and atrial fibrosis in a canine model of chronic obstructive sleep apnea?
Does metoprolol reduce profibrotic remodeling of epicardial adipose tissue and atrial fibrosis in a canine model of chronic obstructive sleep apnea?
Metoprolol attenuates profibrotic remodeling of epicardial adipose tissue and atrial fibrosis in a canine model of chronic OSA, providing experimental evidence for its protective effects against OSA-induced atrial fibrillation.
Hypothesis-generating for metoprolol in OSA-related AF; prospective human trials needed before clinical consideration.
Background Whether chronic obstructive sleep apnea ( OSA ) could promote epicardial adipose tissue ( EAT ) secretion of profibrotic adipokines, and thereby contribute to atrial fibrosis, and the potential therapeutic effects of metoprolol remain unknown. Methods and Results A chronic OSA canine model was established by repeatedly clamping the endotracheal tube for and then reopening it for 4 hours every other day for 12 weeks. In a metoprolol treatment group, metoprolol succinate was administered daily for 12 weeks. The EAT infiltration and left atrial fibrosis were examined. The expressions of adipokines secreted by EAT and hypoxic 3T3-L1 adipocytes were detected. The changes in collagen synthesis, transforming growth factor-β1 expression, and cell differentiation and proliferation in cardiac fibroblasts induced by hypoxic 3T3-L1 adipocyte-derived conditioned medium were further analyzed. Chronic OSA induced infiltration of EAT into the left atrium. OSA enhanced the profibrotic effect of EAT on the adjacent atrial myocardium. Moreover, OSA induced profibrotic cytokine secretion from EAT . We also found that hypoxia induced adipokine secretion in cultured adipocytes, and the medium conditioned by the hypoxic adipocytes increased collagen and transforming growth factor-β1 protein expression and cell proliferation of cardiac fibroblasts. More importantly, metoprolol attenuated infiltration of EAT and alleviated the profibrotic effect of EAT by inhibiting adipokine secretion. Metoprolol also inhibited hypoxia-induced adipokine secretion in adipocytes and thereby blocked the hypoxic adipocyte-derived conditioned medium-induced fibrotic response of cardiac fibroblasts. Conclusions Chronic OSA enhanced the profibrotic effect of EAT on the neighboring atrial myocardium by stimulating the secretion of profibrotic adipokines from EAT , which was significantly attenuated by metoprolol. This study gives insights into mechanisms underlying OSA -induced atrial fibrillation and also provides experimental evidence for the protective effects of metoprolol.
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Dai et al. (2019) studied Chronic Obstructive Sleep Apnea (OSA). Metoprolol succinate vs. Chronic OSA without metoprolol was evaluated on Epicardial adipose tissue (EAT) infiltration, left atrial fibrosis, and adipokine secretion. Metoprolol attenuated epicardial adipose tissue infiltration and alleviated its profibrotic effect on the atrial myocardium by inhibiting adipokine secretion in a canine model of chronic OSA.
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