Center for Lipid Biosciences, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
Lipid Science and Aging Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Int J Mol Sci. 2020 Jan 30;21(3):891. doi: 10.3390/ijms21030891.
Atrial fibrillation (AF) is the most common persistent arrhythmia, and can lead to systemic thromboembolism and heart failure. Aging and metabolic syndrome (MetS) are major risks for AF. One of the most important manifestations of MetS is dyslipidemia, but its correlation with AF is ambiguous in clinical observational studies. Although there is a paradoxical relationship between fasting cholesterol and AF incidence, the beneficial benefit from lipid lowering therapy in reduction of AF is significant. Here, we reviewed the health burden from AF and MetS, the association between two disease entities, and the metabolism of triglyceride, which is elevated in MetS. We also reviewed scientific evidence for the mechanistic links between very low density lipoproteins (VLDL), which primarily carry circulatory triglyceride, to atrial cardiomyopathy and development of AF. The effects of VLDL to atria suggesting pathogenic to atrial cardiomyopathy and AF include excess lipid accumulation, direct cytotoxicity, abbreviated action potentials, disturbed calcium regulation, delayed conduction velocities, modulated gap junctions, and sarcomere protein derangements. The electrical remodeling and structural changes in concert promote development of atrial cardiomyopathy in MetS and ultimately lead to vulnerability to AF. As VLDL plays a major role in lipid metabolism after meals (rather than fasting state), further human studies that focus on the effects/correlation of postprandial lipids to atrial remodeling are required to determine whether VLDL-targeted therapy can reduce MetS-related AF. On the basis of our scientific evidence, we propose a pivotal role of VLDL in MetS-related atrial cardiomyopathy and vulnerability to AF.
心房颤动（AF）是最常见的持续性心律失常，可导致全身性血栓栓塞和心力衰竭。衰老和代谢综合征（MetS）是 AF 的主要危险因素。MetS 的最重要表现之一是血脂异常，但临床观察研究中其与 AF 的相关性并不明确。尽管空腹胆固醇与 AF 发生率之间存在矛盾关系，但降脂治疗降低 AF 的益处是显著的。在这里，我们回顾了 AF 和 MetS 的健康负担、两种疾病实体之间的关联以及在 MetS 中升高的甘油三酯代谢。我们还回顾了极低密度脂蛋白（VLDL）与心房心肌病和 AF 发展之间的机制联系的科学证据，VLDL 主要携带循环中的甘油三酯。VLDL 对心房的作用表明对心房心肌病和 AF 的致病性包括脂质过度积累、直接细胞毒性、动作电位缩短、钙调节紊乱、传导速度延迟、间隙连接调节以及肌节蛋白紊乱。电重构和结构变化协同促进 MetS 中心房心肌病的发展，并最终导致对 AF 的易感性。由于 VLDL 在餐后（而不是空腹状态）的脂质代谢中起主要作用，因此需要进一步的人类研究来确定餐后脂质对心房重构的影响/相关性，以确定 VLDL 靶向治疗是否可以降低与 MetS 相关的 AF。基于我们的科学证据，我们提出 VLDL 在 MetS 相关的心房心肌病和易感性 AF 中起着关键作用。
