自噬在心肌肥厚中的研究进展

MRP

Medical Research and Practice

2993-96902993-9704

Art and Technology

10.61369/MRP.11883

Article

自噬在心肌肥厚中的研究进展https://artdesignp.com/journal/MRP/2/12/10.61369/MRP.11883刘若冰,胡宇峰

2024

212

2024-12-20

自噬是心肌细胞肥大的重要分子机制之一。自噬过程涉及多个层面，包括自噬体的形成、成熟和降解，这些过程在心肌肥厚的发展中起着关键作用。研究显示，自噬在生理性心肌肥厚和病理性心肌肥厚中的作用有所不同。生理性心肌肥厚中，自噬被适度激活，通过清除受损细胞器和错误折叠蛋白，维持心肌细胞稳态。在病理性心肌肥厚中具有双重性：一方面，自噬可能作为一种代偿机制，在心肌肥厚早期发挥保护作用；另一方面，随着疾病进展，自噬的降低可能导致细胞质组件降解减少，从而促进肥厚。过度的自噬可能破坏自噬流的平衡，损伤必要的蛋白质与细胞器，引起细胞凋亡，并推动疾病向失代偿性心衰进展。心肌肥厚,自噬,机制研究

[1]Roth G A, Dorsey H, Decleene N, et al. The global burden of heart failure: a systematic analysis for the global burden of disease study 2021[J]. European Heart Journal,2023, 44(Supplement_2): ehad655.876.[2]Wei X, Jin J, Wu J, et al. Cardiac-specific BACH1 ablation attenuates pathological cardiac hypertrophy by inhibiting the ang II type 1 receptor expression and the Ca2+/CaMKII pathway[J]. Cardiovascular Research, 2023, 119(9): 1842-1855.[3]Rabinovich-Nikitin I, Kirshenbaum E, Kirshenbaum L A. Autophagy, clock genes, and cardiovascular disease[J]. Canadian Journal of Cardiology, 2023, 39(12): 1772-1780.[4]Bai Y, Zhang X, Li Y, et al. Protein kinase a is a master regulator of physiological and pathological cardiac hypertrophy[J]. Circulation Research, 2024, 134(4): 393-410.[5]Ritterhoff J, Tian R. Metabolic mechanisms in physiological and pathological cardiac hypertrophy: new paradigms and challenges[J]. Nature Reviews. Cardiology, 2023,20(12): 812-829.[6] 陈铿铨, 王忠芹, 刘超, 等. 1- 磷酸鞘胺醇通过其受体3 改善压力超负荷诱导的病理性心肌肥厚[J]. 中国心血管杂志, 2022, 27(5): 459-467.[7]张勇涛, 蒋凡. 生理性和病理性心肌肥厚的信号传导机制[J]. 中华心血管病杂志, 2015, 43(3): 277-280.[8]Prinzen F W, Auricchio A, Mullens W, 等. Electrical management of heart failure: from pathophysiology to treatment[J]. European Heart Journal, 2022, 43(20): 1917-1927.[9] 朱峰. 《中国成人肥厚型心肌病诊断与治疗指南2023》要点解读[J]. 临床心血管病杂志, 2023, 39(6): 413-416.[10]Nishimura R A, Seggewiss H, Schaff H V. Hypertrophic obstructive cardiomyopathy[J]. Circulation Research, 2017, 121(7): 771-783.[11] 田庄, 张抒扬. 《中国心力衰竭诊断和治疗指南2024》要点解读[J]. 协和医学杂志, 2024, 15(4): 801-806.[12] 关开行, 王文景, 姜允奇, 等. β 肾上腺素受体在心血管系统的基础与临床研究进展[J]. 中国心血管杂志, 2019, 24(5): 399-403.[13] 杨昭, 杨旭明, 杜来景. Mavacamten特异性治疗肥厚型心肌病的研究进展[J]. 临床心血管病杂志, 2022, 38(4): 267-271.[14]Liu S, Yao S, Yang H, et al. Autophagy: Regulator of cell death[J]. Cell Death & Disease, 2023, 14(10): 648.[15]Wang L, Klionsky D J, Shen H M. The emerging mechanisms and functions of microautophagy[J]. Nature Reviews Molecular Cell Biology, 2023, 24(3): 186-203.[16]He W, Hu C X, Hou J K, et al. Microtubule-associated protein 1 light chain 3 interacts with and contributes to growth inhibiting effect of PML[J]. PLOS One, 2014, 9(11):e113089.[17]Russell R C, Guan K L. The multifaceted role of autophagy in cancer[J]. EMBO Journal, 2022, 41(13): e110031.[18] 张学文, 吴念平. Beclin1在自噬中的作用机制及其蛋白修饰的研究进展[J]. 中国生物制品学杂志, 2023, 36(6): 751-758,763.[19] 施诚龙, 陈冲, 高永军, 等. PI3K/AKT/mTOR信号通路在细胞自噬中作用及机制的研究进展[J]. 山东医药, 2021, 61(27): 102-105.[20]Zhao Y G, Codogno P, Zhang H. Machinery, regulation and pathophysiological implications of autophagosome maturation[J]. Nature Reviews. Molecular Cell Biology,2021, 22(11): 733-750.[21]Ruan P, Zheng Y, Dong Z, et al. [research progress in the regulation of autophagy and mitochondrial homeostasis by AMPK signaling channels][J]. Zhonghua Wei ZhongBing Ji Jiu Yi Xue, 2024, 36(4): 425-429.[22]Filippone A, Esposito E, Mannino D, et al. The contribution of altered neuronal autophagy to neurodegeneration[J]. Pharmacology & Therapeutics, 2022, 238: 108178.[23] 高展旺, 张昕, 王羚郦. 基于调节自噬的中药及其复方抗心肌肥厚的研究进展[J]. 中成药, 2023, 45(12): 4042-4048.[24]Xu C N, Kong L H, Ding P, et al. Melatonin ameliorates pressure overload-induced cardiac hypertrophy by attenuating Atg5-dependent autophagy and activating the akt/mTOR pathway[J]. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2020, 1866(10): 165848.[25]Xu Z, Jin Y, Gao Z, et al. Autophagic degradation of CCN2 (cellular communication network factor 2) causes cardiotoxicity of sunitinib[J]. Autophagy, 2022, 18(5): 1152-1173.[26] 胡欢, 李萍, 程晓曙. 线粒体功能障碍与心肌肥厚的研究进展[J]. 重庆医学, 2018, 47(23): 3081-3083.[27]潘月顺, 仇琪. 不同负荷运动训练对慢性心力衰竭大鼠心功能及自噬相关蛋白表达的影响[J]. 中国运动医学杂志, 2020, 39(2): 133-137.[28] 陈志强, 邓勇志. mTOR信号通路与心血管疾病的研究进展[J]. 中华临床医师杂志（电子版）, 2013(8): 3504-3506.[29]Li A, Gao M, Liu B, et al. Mitochondrial autophagy: molecular mechanisms and implications for cardiovascular disease[J]. Cell Death & Disease, 2022, 13(5): 444.[30]Ljubojević-Holzer S, Kraler S, Djalinac N, et al. Loss of autophagy protein ATG5 impairs cardiac capacity in mice and humans through diminishing mitochondrial abundanceand disrupting Ca2+ cycling[J]. Cardiovascular Research, 2022, 118(6): 1492-1505.[31] 丁晓青, 马春伟, 高炳宏. SIRT3 调节病理性心肌线粒体自噬的研究进展[J]. 生命科学, 2022, 34(07): 848-854.[32] 杨资鉴, 秦富忠. mTOR信号通路在缺血性心脏病中的研究进展[J]. 中国当代医药, 2016, 23(33): 16-19.[33]Qiang Z, Jin B, Peng Y, et al. miR-762 modulates thyroxine-induced cardiomyocyte hypertrophy by inhibiting Beclin-1[J]. Endocrine, 2019, 66(3): 585-595.[34]Agbo E, Li M X, Wang Y Q, et al. Hexarelin protects cardiac H9C2 cells from angiotensin II-induced hypertrophy via the regulation of autophagy[J]. Die Pharmazie, 2019,74(8): 485-491.[35]Li J, Cai Y. The dual effects of autophagy in myocardial hypertrophy[J]. Acta Cardiologica, 2015, 70(4): 493-498.[36] 李渊芳, 谢盈彧, 徐士欣, 等. 线粒体自噬与心脏能量代谢研究进展[J]. 中华老年心脑血管病杂志, 2019, 21(3): 320-323.[37]Fernández Á F, Sebti S, Wei Y, et al. Disruption of the beclin 1–BCL2 autophagy regulatory complex promotes longevity in mice[J]. Nature, 2018, 558(7708): 136-140.[38]Feng Y, Chen Y, Wu X, et al. Interplay of energy metabolism and autophagy[J]. Autophagy, 2024, 20(1): 4-14.[39] 张哲, 王杏, 杨林泉, 等. 利拉鲁肽通过调控AMPK/mTOR自噬信号减轻糖尿病大鼠心肌炎症和氧化应激损伤[J]. 中国药理学通报, 2022, 38(9): 1308-1314.