Department of Pharmacology, 2358University of Virginia, Charlottesville, VA, USA.
Institute of Pharmacology and Clinical Pharmacology, 9170Heinrich Heine University, Düsseldorf, Germany.
J Cardiovasc Pharmacol Ther. 2021 May;26(3):289-297. doi: 10.1177/1074248420971113. Epub 2020 Nov 5.
The pathological role of adipose derived fatty acids following myocardial infarction has long been hypothesized. However, most methods for reducing adipocyte lipolysis have significant non-adipose effects. Atglistatin, a direct inhibitor of the initial lipase in the lipolysis cascade, has been recently shown to inhibit adipose tissue lipolysis after oral administration. To explore the ability of Atglistatin to impact the pathophysiology of cardiac ischemia we performed prophylactic treatment of mice with Atglistatin for 2 days before 1-hour cardiac ischemia. After 7 days of reperfusion, hearts of Atglistatin treated mice showed significantly improved systolic pump function while infarct and scar size were unaffected. Strain analysis of echocardiographic data revealed an enhanced performance of the remote myocardium as cause for overall improved systolic function. The present study provides evidence that inhibition of adipocyte adipose triglyceride lipase (ATGL) using Atglistatin is able to improve cardiac function after MI by targeting the remote myocardium.
脂肪衍生脂肪酸在心肌梗死后的病理作用早已被假设。然而，大多数减少脂肪细胞脂肪分解的方法都有明显的非脂肪作用。Atglistatin 是脂肪分解级联反应中初始脂肪酶的直接抑制剂，最近已被证明可在口服后抑制脂肪组织脂肪分解。为了探讨 Atglistatin 对心肌缺血病理生理学的影响，我们在 1 小时心肌缺血前对小鼠进行了 2 天的预防性治疗。在 7 天的再灌注后，Atglistatin 治疗组小鼠的心脏收缩泵功能明显改善，而梗死和疤痕大小不受影响。超声心动图数据的应变分析显示，远程心肌的性能增强是整体收缩功能改善的原因。本研究提供的证据表明，使用 Atglistatin 抑制脂肪细胞脂肪甘油三酯脂肪酶（ATGL）可通过靶向远程心肌来改善 MI 后的心脏功能。
