|
|
组蛋白去乙酰化酶3：腹主动脉瘤治疗新靶点？
|
Abstract:
组蛋白去乙酰化酶是一组能调节组蛋白和非组蛋白赖氨酸残基去乙酰化的酶类，在染色体的结构修饰和基因表达调控发挥着重要的作用。近年来随着对组蛋白去乙酰化酶3研究不断深入，发现其与腹主动脉瘤有着密切关系。腹主动脉瘤是多种原因导致动脉中层结构破坏的动脉扩张性疾病，主要发病机制为细胞外基质破坏性重构、血管平滑肌细胞凋亡、炎症与氧化应激等。而组蛋白去乙酰化酶3可能通过上述途径参与腹主动脉瘤的发生发展。因此，本文通过对组蛋白去乙酰化酶3和腹主动脉瘤的致病机制进行综述，为腹主动脉瘤的治疗提供新思路和新靶点。
Histone deacetylases are a group of enzymes that can regulate the deacetylation of histone and non-histone lysine residues, and play an important role in chromosome structural modification and gene expression regulation. In recent years, with the deepening of research on histone deacetylase 3, it has been found that it is closely related to abdominal aortic aneurysm. Abdominal aortic aneurysm is a kind of arterial dilatation disease that causes the destruction of the middle layer of the artery. The main pathogenesis is the destructive remodeling of the extracellular matrix, the apoptosis of vascular smooth muscle cells, inflammation and oxidative stress. Histone deacetylase 3 may be involved in the development of abdominal aortic aneurysm through the above pathways. Therefore, this article provides a new idea and a new target for the treatment of abdominal aortic aneurysm by summarizing the pathogenic mechanism of histone deacetylase 3 and abdominal aortic aneurysm.
| [1] | 张江锋, 覃晓. 腹主动脉瘤发病机制的研究[J]. 广西医科大学学报, 2020, 37(2): 309-314. |
| [2] | Emmett, M.J. and Lazar, M.A. (2018) Integrative Regulation of Physiology by Histone Deacetylase 3. Nature Reviews Molecular Cell Biology, 20, 102-115. https://doi.org/10.1038/s41580-018-0076-0 |
| [3] | 龙殿飞, 李娜, 薛世珊, 等. 组蛋白去乙酰化酶抑制剂在心血管疾病中的治疗潜力[J]. 心血管病学进展, 2021, 42(10): 933-936. |
| [4] | 蒋佳文, 李善高. 组蛋白去乙酰化酶与炎症性疾病[J]. 浙江医学, 2024, 46(7): 776-780. |
| [5] | 吴佳, 王海洋. 腹主动脉瘤的发病机制研究进展[J]. 医学综述, 2019, 25(6): 1110-1116. |
| [6] | Krishna, S.M., Dear, A.E., Norman, P.E. and Golledge, J. (2010) Genetic and Epigenetic Mechanisms and Their Possible Role in Abdominal Aortic Aneurysm. Atherosclerosis, 212, 16-29. https://doi.org/10.1016/j.atherosclerosis.2010.02.008 |
| [7] | Accarino, G., Giordano, A.N., Falcone, M., Celano, A., Vassallo, M.G., Fornino, G., et al. (2023) Abdominal Aortic Aneurysm: Natural History, Pathophysiology and Translational Perspectives. Translational Medicine UniSa, 24, Article 6. https://doi.org/10.37825/2239-9747.1037 |
| [8] | Branchetti, E., Poggio, P., Sainger, R., Shang, E., Grau, J.B., Jackson, B.M., et al. (2013) Oxidative Stress Modulates Vascular Smooth Muscle Cell Phenotype via CTGF in Thoracic Aortic Aneurysm. Cardiovascular Research, 100, 316-324. https://doi.org/10.1093/cvr/cvt205 |
| [9] | Petsophonsakul, P., Furmanik, M., Forsythe, R., Dweck, M., Schurink, G.W., Natour, E., et al. (2019) Role of Vascular Smooth Muscle Cell Phenotypic Switching and Calcification in Aortic Aneurysm Formation. Arteriosclerosis, Thrombosis, and Vascular Biology, 39, 1351-1368. https://doi.org/10.1161/atvbaha.119.312787 |
| [10] | Okamoto, H., Fujioka, Y., Takahashi, A., Takahashi, T., Taniguchi, T., Ishikawa, Y., et al. (2006) Trichostatin A, an Inhibitor of Histone Deacetylase, Inhibits Smooth Muscle Cell Proliferation via Induction of P21WAF1. Journal of Atherosclerosis and Thrombosis, 13, 183-191. https://doi.org/10.5551/jat.13.183 |
| [11] | Li, X., Chen, M., Chen, X., He, X., Li, X., Wei, H., et al. (2024) TRAP1 Drives Smooth Muscle Cell Senescence and Promotes Atherosclerosis via HDAC3-Primed Histone H4 Lysine 12 Lactylation. European Heart Journal, 45, 4219-4235. https://doi.org/10.1093/eurheartj/ehae379 |
| [12] | McDonald, O.G. and Owens, G.K. (2007) Programming Smooth Muscle Plasticity with Chromatin Dynamics. Circulation Research, 100, 1428-1441. https://doi.org/10.1161/01.res.0000266448.30370.a0 |
| [13] | Zhong, X., Wei, X., Xu, Y., Zhu, X., Huo, B., Guo, X., et al. (2024) The Lysine Methyltransferase SMYD2 Facilitates Neointimal Hyperplasia by Regulating the HDAC3-SRF Axis. Acta Pharmaceutica Sinica B, 14, 712-728. https://doi.org/10.1016/j.apsb.2023.11.012 |
| [14] | Sun, J., Deng, H., Zhou, Z., Xiong, X. and Gao, L. (2018) Endothelium as a Potential Target for Treatment of Abdominal Aortic Aneurysm. Oxidative Medicine and Cellular Longevity, 2018, Article 6306542. https://doi.org/10.1155/2018/6306542 |
| [15] | 李双月, 刘淇麒, 冯馨锐, 等. 组蛋白去乙酰化酶3与血管内皮细胞的关系[J]. 吉林医药学院学报, 2018, 39(3): 201-203. |
| [16] | Zampetaki, A., Zeng, L., Margariti, A., Xiao, Q., Li, H., Zhang, Z., et al. (2010) Histone Deacetylase 3 Is Critical in Endothelial Survival and Atherosclerosis Development in Response to Disturbed Flow. Circulation, 121, 132-142. https://doi.org/10.1161/circulationaha.109.890491 |
| [17] | Wang, Y., Chen, T., Yan, H., Qi, H., Deng, C., Ye, T., et al. (2013) Role of Histone Deacetylase Inhibitors in the Aging of Human Umbilical Cord Mesenchymal Stem Cells. Journal of Cellular Biochemistry, 114, 2231-2239. https://doi.org/10.1002/jcb.24569 |
| [18] | Pons, D., de Vries, F.R., van den Elsen, P.J., Heijmans, B.T., Quax, P.H.A. and Jukema, J.W. (2008) Epigenetic Histone Acetylation Modifiers in Vascular Remodelling: New Targets for Therapy in Cardiovascular Disease. European Heart Journal, 30, 266-277. https://doi.org/10.1093/eurheartj/ehn603 |
| [19] | Márquez-Sánchez, A.C. and Koltsova, E.K. (2022) Immune and Inflammatory Mechanisms of Abdominal Aortic Aneurysm. Frontiers in Immunology, 13, Article 989933. https://doi.org/10.3389/fimmu.2022.989933 |
| [20] | Li, J., Zhai, Y. and Tang, M. (2024) Integrative Function of Histone Deacetylase 3 in Inflammation. Molecular Biology Reports, 51, Article No. 83. https://doi.org/10.1007/s11033-023-09077-x |
| [21] | DiDonato, J.A., Mercurio, F. and Karin, M. (2012) NF‐κB and the Link between Inflammation and Cancer. Immunological Reviews, 246, 379-400. https://doi.org/10.1111/j.1600-065x.2012.01099.x |
| [22] | Saito, T., Hasegawa, Y., Ishigaki, Y., Yamada, T., Gao, J., Imai, J., et al. (2012) Importance of Endothelial NF-κB Signalling in Vascular Remodelling and Aortic Aneurysm Formation. Cardiovascular Research, 97, 106-114. https://doi.org/10.1093/cvr/cvs298 |
| [23] | Leus, N.G., Zwinderman, M.R. and Dekker, F.J. (2016) Histone Deacetylase 3 (HDAC 3) as Emerging Drug Target in NF-κB-Mediated Inflammation. Current Opinion in Chemical Biology, 33, 160-168. https://doi.org/10.1016/j.cbpa.2016.06.019 |
| [24] | Travers, J.G., Wennersten, S.A., Peña, B., Bagchi, R.A., Smith, H.E., Hirsch, R.A., et al. (2021) HDAC Inhibition Reverses Preexisting Diastolic Dysfunction and Blocks Covert Extracellular Matrix Remodeling. Circulation, 143, 1874-1890. https://doi.org/10.1161/circulationaha.120.046462 |
| [25] | Lazaropoulos, M.P. and Elrod, J.W. (2023) Cardiac Fibrosis Mitigated by an Endogenous Negative Regulator of HDAC. Circulation Research, 133, 252-254. https://doi.org/10.1161/circresaha.123.323211 |
| [26] | Joviliano, E.E., Ribeiro, M.S. and Tenorio, E.J.R. (2017) MicroRNAs and Current Concepts on the Pathogenesis of Abdominal Aortic Aneurysm. Brazilian Journal of Cardiovascular Surgery, 32, 215-224. https://doi.org/10.21470/1678-9741-2016-0050 |
| [27] | 唐红悦, 刘欣, 向紫萍, 等. miR-10b-5p在腹主动脉瘤患者血清的表达及临床意义[J]. 江苏医药, 2024, 50(7): 657-661. |
| [28] | Jing, J., Chang, M., Jiang, S., Wang, T., Sun, Q., Yang, J., et al. (2023) Clinical Value of Serum miR-1-3p as a Potential Circulating Biomarker for Abdominal Aortic Aneurysm. Annals of Medicine, 55, Article 2260395. https://doi.org/10.1080/07853890.2023.2260395 |
| [29] | Boon, R.A. and Dimmeler, S. (2011) Micrornas and Aneurysm Formation. Trends in Cardiovascular Medicine, 21, 172-177. https://doi.org/10.1016/j.tcm.2012.05.005 |
| [30] | Ji, L., Chen, S., Gu, G., Wang, W., Ren, J., Xu, F., et al. (2021) Discovery of Potential Biomarkers for Human Atherosclerotic Abdominal Aortic Aneurysm through Untargeted Metabolomics and Transcriptomics. Journal of Zhejiang University-SCIENCE B, 22, 733-745. https://doi.org/10.1631/jzus.b2000713 |
| [31] | Toghill, B.J., Saratzis, A. and Bown, M.J. (2017) Abdominal Aortic Aneurysm—An Independent Disease to Atherosclerosis? Cardiovascular Pathology, 27, 71-75. https://doi.org/10.1016/j.carpath.2017.01.008 |
| [32] | Jiang, L., Yu, X., Chen, J., Hu, M., Zhang, Y., Lin, H., et al. (2022) Histone Deacetylase 3: A Potential Therapeutic Target for Atherosclerosis. Aging and disease, 13, 773-786. https://doi.org/10.14336/ad.2021.1116 |
| [33] | Hoeksema, M.A., Gijbels, M.J., Van den Bossche, J., van der Velden, S., Sijm, A., Neele, A.E., et al. (2014) Targeting Macrophage Histone Deacetylase 3 Stabilizes Atherosclerotic Lesions. EMBO Molecular Medicine, 6, 1124-1132. https://doi.org/10.15252/emmm.201404170 |
| [34] | Yu, X., Deng, W., Chen, J., Xu, X., Liu, X., Chen, L., et al. (2020) LncRNA kcnq1ot1 Promotes Lipid Accumulation and Accelerates Atherosclerosis via Functioning as a ceRNA through the miR-452-3p/HDAC3/ABCA1 Axis. Cell Death & Disease, 11, Article No. 1043. https://doi.org/10.1038/s41419-020-03263-6 |
| [35] | Singh, B., Cui, K., Eisa-Beygi, S., Zhu, B., Cowan, D.B., Shi, J., et al. (2024) Elucidating the Crosstalk between Endothelial-to-Mesenchymal Transition (EndoMT) and Endothelial Autophagy in the Pathogenesis of Atherosclerosis. Vascular Pharmacology, 155, Article 107368. https://doi.org/10.1016/j.vph.2024.107368 |
| [36] | Chen, L., Shang, C., Wang, B., Wang, G., Jin, Z., Yao, F., et al. (2021) HDAC3 Inhibitor Suppresses Endothelial-to-Mesenchymal Transition via Modulating Inflammatory Response in Atherosclerosis. Biochemical Pharmacology, 192, Article 114716. https://doi.org/10.1016/j.bcp.2021.114716 |
| [37] | Dinarello, C.A., Fossati, G. and Mascagni, P. (2011) Histone Deacetylase Inhibitors for Treating a Spectrum of Diseases Not Related to Cancer. Molecular Medicine, 17, 333-352. https://doi.org/10.2119/molmed.2011.00116 |
