Departament de Bioquímica i Biologia Molecular, Institut de Biomedicina de la Universitat de Barcelona (IBUB) i Institut de Recerca Sant Joan de Deu (IRSJD), Universitat de Barcelona, Barcelona, Spain.
CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Madrid, Spain.
J Pathol. 2021 Feb;253(2):198-208. doi: 10.1002/path.5573. Epub 2020 Nov 26.
Alcoholic cardiomyopathy (ACM) resulting from chronic alcohol misuse is one of the main contributors leading to heart failure and cardiovascular mortality. Fibroblast growth factor 21 (FGF21) is a well-established cardioprotective factor. We aimed to study the role of FGF21 in experimentally induced models and clinical affected patients with cardiac damage due to chronic alcohol consumption. We found that circulating FGF21 levels and cardiac FGF21 and β-klotho protein levels were increased in subjects with chronic alcohol consumption. As an experimental model of ACM, we fed wild-type and Fgf21 knockout (Fgf21 ) mice with a 4% alcohol liquid diet for 4 and 12 weeks. FGF21 circulating levels and FGF21 expression in the myocardium were also increased in wild-type mice after chronic alcohol intake. Fgf21 mice develop a higher degree of cardiac hypertrophy, fibrosis, and cardiac dysfunction after chronic alcohol consumption than wild-type mice. Moreover, the myocardium of Fgf21 mice showed signs of metabolic deregulation, oxidative stress, and mitochondrial dysfunction after alcohol intake. Finally, human cardiac biopsies from patients with chronic alcohol consumption developing ACM presented a higher degree of oxidative stress which positively correlated with the FGF21 protein levels in the myocardium. We conclude that plasma levels and cardiac myocyte FGF21 expression were induced in response to chronic alcohol consumption. The lack of FGF21 aggravated cardiac damage produced by ACM, in association with enhanced mitochondrial and oxidative stress, thus pointing to FGF21 as a protective agent against development of alcohol-induced cardiomyopathy. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
酒精性心肌病（ACM）是由慢性酒精滥用引起的，是导致心力衰竭和心血管死亡率的主要原因之一。成纤维细胞生长因子 21（FGF21）是一种公认的心脏保护因子。我们旨在研究 FGF21 在实验诱导的模型和临床受影响的患者中的作用，这些患者由于慢性酒精消费而导致心脏损伤。我们发现，慢性酒精消费的受试者的循环 FGF21 水平以及心脏 FGF21 和β-klotho 蛋白水平升高。作为 ACM 的实验模型，我们用 4%酒精液体饮食喂养野生型和 Fgf21 敲除（Fgf21）小鼠 4 周和 12 周。慢性酒精摄入后，野生型小鼠的循环 FGF21 水平和心肌 FGF21 表达也增加。与野生型小鼠相比，Fgf21 小鼠在慢性酒精摄入后会发展出更高程度的心肌肥大、纤维化和心功能障碍。此外，酒精摄入后，Fgf21 小鼠的心肌表现出代谢失调、氧化应激和线粒体功能障碍的迹象。最后，来自慢性酒精消耗发展为 ACM 的患者的人类心脏活检显示出更高程度的氧化应激，与心肌中 FGF21 蛋白水平呈正相关。我们得出结论，血浆水平和心肌细胞 FGF21 表达是对慢性酒精消费的反应而诱导的。缺乏 FGF21 加重了 ACM 引起的心脏损伤，与增强的线粒体和氧化应激有关，因此表明 FGF21 是预防酒精性心肌病发展的保护剂。©2020 大不列颠及爱尔兰病理学学会。由 John Wiley & Sons，Ltd. 出版。
