Yu Wei, Chen Chunjuan, Cheng Jidong
Department of Internal Medicine, Xiang'an Hospital of Xiamen University, Xiamen, 361102, China.
Department of Cardiology, Second Affiliated Hospital of Shantou University Medical College, 69 Dong Xia North Road, Shantou, 515041, China.
ESC Heart Fail. 2020 Dec;7(6):3497-3504. doi: 10.1002/ehf2.13065. Epub 2020 Oct 22.
Cardiac hypertrophy can lead to heart failure and cardiovascular events and has become a research hotspot in the field of cardiovascular disease. Despite extensive and in-depth research, the pathogenesis of cardiac hypertrophy is far from being fully understood. Increasing evidence has shown that the transcription factor forkhead box protein O 1 (FoxO1) is closely related to the occurrence and development of cardiac hypertrophy. This review summarizes the current literature on the role and molecular mechanism of FoxO1 in cardiac hypertrophy. We searched the database MEDLINE via PubMed for available evidence on the effect of FoxO1 on cardiac hypertrophy. FoxO1 has many effects on multiple diseases, including cardiovascular diseases, diabetes, cancer, aging, and stem cell activity. Recent studies have shown that FoxO1 plays a critical role in the development of cardiac hypertrophy. Evidence for this relationship includes the following. (i) FoxO1 can regulate cardiac growth/protein synthesis, calcium homeostasis, cell apoptosis, and autophagy and (ii) is controlled by several upstream signalling molecules (e.g. phosphatidylinositol 3-kinase/Akt, AMP-activated protein kinase, and sirtuins) and regulates many downstream transcription proteins (e.g. ubiquitin ligases muscle RING finger 1/muscle atrophy F-box, calcineurin/nuclear factor of activated T cells, and microRNAs). In response to stress or external stimulation (e.g. low energy, oxidative stress, or growth factor signalling), FoxO1 undergoes post-translational modification and transfers from the cytoplasm to nucleus, thus regulating the expression of a series of target genes in myocardium that are involved in cardiac growth/protein synthesis, calcium homeostasis, cell apoptosis, and autophagy. (iii) Finally, targeted regulation of FoxO1 is an effective method of intervening in myocardial hypertrophy. The information reviewed here should be significant for understanding the roles of FoxO1 in cardiac hypertrophy and should contribute to the design of further studies related to FoxO1 and the hypertrophic response. It should also shed light on a potential treatment for cardiac hypertrophy.
心肌肥厚可导致心力衰竭和心血管事件，已成为心血管疾病领域的研究热点。尽管进行了广泛而深入的研究，但心肌肥厚的发病机制仍远未完全阐明。越来越多的证据表明，转录因子叉头框蛋白O 1（FoxO1）与心肌肥厚的发生发展密切相关。本综述总结了目前关于FoxO1在心肌肥厚中的作用及分子机制的文献。我们通过PubMed在MEDLINE数据库中搜索了有关FoxO1对心肌肥厚影响的现有证据。FoxO1对多种疾病有诸多影响，包括心血管疾病、糖尿病、癌症、衰老及干细胞活性。最近的研究表明，FoxO1在心肌肥厚的发展中起关键作用。这种关系的证据如下：（i）FoxO1可调节心脏生长/蛋白质合成、钙稳态、细胞凋亡和自噬；（ii）受几种上游信号分子（如磷脂酰肌醇3激酶/Akt、AMP激活的蛋白激酶和沉默调节蛋白）调控，并调节许多下游转录蛋白（如泛素连接酶肌肉环指蛋白1/肌肉萎缩F盒、钙调神经磷酸酶/活化T细胞核因子和微小RNA）。在应激或外部刺激（如低能量、氧化应激或生长因子信号）作用下，FoxO1发生翻译后修饰并从细胞质转移至细胞核，从而调节心肌中一系列参与心脏生长/蛋白质合成、钙稳态、细胞凋亡和自噬的靶基因的表达。（iii）最后，对FoxO1进行靶向调控是干预心肌肥厚的有效方法。本文综述的信息对于理解FoxO1在心肌肥厚中的作用具有重要意义，应有助于设计与FoxO1及肥厚反应相关的进一步研究。它还应为心肌肥厚的潜在治疗提供线索。
