Charité - Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Pharmacology, Center for Cardiovascular Research, Berlin, Germany.
DZHK (German Centre for Cardiovascular Research), Berlin, Germany.
Cell Rep Med. 2020 Mar 25;1(1):100001. doi: 10.1016/j.xcrm.2020.100001. eCollection 2020 Apr 21.
Heart failure is one of the leading causes of death worldwide. New therapeutic concepts are urgently required to lower the burden of heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), the two major forms of heart failure. Lipolytic processes are induced during the development of heart failure and occur in adipose tissue and multiple organs, including the heart. Increasing evidence suggests that cellular lipolysis, in particular, adipose triglyceride lipase (ATGL) activity, has an important function in cardiac (patho)physiology. This review summarizes the crucial role of cellular lipolysis for normal cardiac function and for the development of HFrEF and HFpEF. We discuss the most relevant pre-clinical studies and elaborate on the cardiac consequences of non-myocardial and myocardial lipolysis modulation. Finally, we critically analyze the therapeutic importance of pharmacological ATGL inhibition as a potential treatment option for HFrEF and/or HFpEF in the future.
心力衰竭是全球范围内导致死亡的主要原因之一。迫切需要新的治疗理念来降低射血分数降低型心力衰竭（HFrEF）和射血分数保留型心力衰竭（HFpEF）的负担，这两种心力衰竭是心力衰竭的两种主要形式。在心力衰竭的发展过程中会诱导脂肪分解过程，并发生在脂肪组织和包括心脏在内的多个器官中。越来越多的证据表明，细胞脂肪分解，特别是脂肪甘油三酯脂肪酶（ATGL）活性，在心（病理）生理学中具有重要功能。本综述总结了细胞脂肪分解对正常心脏功能以及 HFrEF 和 HFpEF 发展的关键作用。我们讨论了最相关的临床前研究，并详细阐述了非心肌和心肌脂肪分解调节的心脏后果。最后，我们批判性地分析了药理学 ATGL 抑制作为未来 HFrEF 和/或 HFpEF 潜在治疗选择的治疗重要性。
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