Histone Deacetylase 6 as a Novel Promising Target to Treat Cardiovascular Disease

Overview

Journal Cancer Innov

Specialty Biomedical Engineering

Date 2024 Jul 1

PMID 38947757

Authors

Ya-Xi Wu

Bing-Qian Li

Xiao-Qian Yu

Yu-Lin Liu

Rui-Hao Chui

Kai Sun

Dian-Guang Geng

Li-Ying Ma

Affiliations

Soon will be listed here.

Abstract

Histone deacetylase 6 (HDAC6) belongs to a class of epigenetic targets that have been found to be a key protein in the association between tumors and cardiovascular disease. Recent studies have focused on the crucial role of HDAC6 in regulating cardiovascular diseases such as atherosclerosis, myocardial infarction, myocardial hypertrophy, myocardial fibrosis, hypertension, pulmonary hypertension, and arrhythmia. Here, we review the association between HDAC6 and cardiovascular disease, the research progress of HDAC6 inhibitors in the treatment of cardiovascular disease, and discuss the feasibility of combining HDAC6 inhibitors with other therapeutic agents to treat cardiovascular disease.

References

Thuny F, Naidoo J, Neilan T . Cardiovascular complications of immune checkpoint inhibitors for cancer. Eur Heart J. 2022; 43(42):4458-4468. PMC: 10263267. DOI: 10.1093/eurheartj/ehac456. View

Nicolls M, Taraseviciene-Stewart L, Rai P, Badesch D, Voelkel N . Autoimmunity and pulmonary hypertension: a perspective. Eur Respir J. 2005; 26(6):1110-8. DOI: 10.1183/09031936.05.00045705. View

Zhang D, Wu C, Qi X, Meijering R, Hoogstra-Berends F, Tadevosyan A . Activation of histone deacetylase-6 induces contractile dysfunction through derailment of α-tubulin proteostasis in experimental and human atrial fibrillation. Circulation. 2013; 129(3):346-58. DOI: 10.1161/CIRCULATIONAHA.113.005300. View

Ho T, Chan A, Ganesan A . Thirty Years of HDAC Inhibitors: 2020 Insight and Hindsight. J Med Chem. 2020; 63(21):12460-12484. DOI: 10.1021/acs.jmedchem.0c00830. View

Zeleke T, Pan Q, Chiuzan C, Onishi M, Li Y, Tan H . Network-based assessment of HDAC6 activity predicts preclinical and clinical responses to the HDAC6 inhibitor ricolinostat in breast cancer. Nat Cancer. 2022; 4(2):257-275. PMC: 9992270. DOI: 10.1038/s43018-022-00489-5. View

Gaowa S, Zhou W, Yu L, Zhou X, Liao K, Yang K . Effect of Th17 and Treg axis disorder on outcomes of pulmonary arterial hypertension in connective tissue diseases. Mediators Inflamm. 2014; 2014:247372. PMC: 4158110. DOI: 10.1155/2014/247372. View

Tao H, Yang J, Hu W, Shi K, Li J . HDAC6 Promotes Cardiac Fibrosis Progression through Suppressing RASSF1A Expression. Cardiology. 2015; 133(1):18-26. DOI: 10.1159/000438781. View

Kee H, Bae E, Park S, Lee K, Suh S, Kim S . HDAC inhibition suppresses cardiac hypertrophy and fibrosis in DOCA-salt hypertensive rats via regulation of HDAC6/HDAC8 enzyme activity. Kidney Blood Press Res. 2013; 37(4-5):229-39. DOI: 10.1159/000350148. View

Nomura Y, Nakano M, Sung H, Han M, Pandey D . Inhibition of HDAC6 Activity Protects Against Endothelial Dysfunction and Atherogenesis : A Role for HDAC6 Neddylation. Front Physiol. 2021; 12:675724. PMC: 8245780. DOI: 10.3389/fphys.2021.675724. View

10.

Zhang D, Hu X, Henning R, Brundel B . Keeping up the balance: role of HDACs in cardiac proteostasis and therapeutic implications for atrial fibrillation. Cardiovasc Res. 2015; 109(4):519-26. DOI: 10.1093/cvr/cvv265. View

11.

Totzeck M, Schuler M, Stuschke M, Heusch G, Rassaf T . Cardio-oncology - strategies for management of cancer-therapy related cardiovascular disease. Int J Cardiol. 2019; 280:163-175. DOI: 10.1016/j.ijcard.2019.01.038. View

12.

Bulut I, Lee A, Cevatemre B, Ruzic D, Belle R, Kawamura A . Dual LSD1 and HDAC6 Inhibition Induces Doxorubicin Sensitivity in Acute Myeloid Leukemia Cells. Cancers (Basel). 2022; 14(23). PMC: 9737972. DOI: 10.3390/cancers14236014. View

13.

Lin C, Hsu K, HuangFu W, Lin T, Huang H, Pan S . Investigating the potential effects of selective histone deacetylase 6 inhibitor ACY1215 on infarct size in rats with cardiac ischemia-reperfusion injury. BMC Pharmacol Toxicol. 2020; 21(1):21. PMC: 7077123. DOI: 10.1186/s40360-020-0400-0. View

14.

Ladak I, Preti B, Dias B, Breadner D . Raltitrexed as a substitute for capecitabine in metastatic gastric cancer: a case report and literature review. Ann Transl Med. 2023; 10(23):1285. PMC: 9816848. DOI: 10.21037/atm-2022-69. View

15.

Somanna N, Valente A, Krenz M, McDonald K, Higashi Y, Noda M . Histone deacetyltransferase inhibitors Trichostatin A and Mocetinostat differentially regulate MMP9, IL-18 and RECK expression, and attenuate Angiotensin II-induced cardiac fibroblast migration and proliferation. Hypertens Res. 2016; 39(10):709-716. DOI: 10.1038/hr.2016.54. View

16.

Zhang L, Deng M, Lu A, Chen Y, Chen Y, Wu C . Sodium butyrate attenuates angiotensin II-induced cardiac hypertrophy by inhibiting COX2/PGE2 pathway via a HDAC5/HDAC6-dependent mechanism. J Cell Mol Med. 2019; 23(12):8139-8150. PMC: 6850921. DOI: 10.1111/jcmm.14684. View

17.

Vaidya G, Rana P, Venkatesh A, Chatterjee D, Contractor D, Satpute D . Paradigm shift of "classical" HDAC inhibitors to "hybrid" HDAC inhibitors in therapeutic interventions. Eur J Med Chem. 2020; 209:112844. DOI: 10.1016/j.ejmech.2020.112844. View

18.

Pulya S, Amin S, Adhikari N, Biswas S, Jha T, Ghosh B . HDAC6 as privileged target in drug discovery: A perspective. Pharmacol Res. 2020; 163:105274. DOI: 10.1016/j.phrs.2020.105274. View

19.

Bertos N, Gilquin B, Chan G, Yen T, Khochbin S, Yang X . Role of the tetradecapeptide repeat domain of human histone deacetylase 6 in cytoplasmic retention. J Biol Chem. 2004; 279(46):48246-54. DOI: 10.1074/jbc.M408583200. View

20.

Li P, Ge J, Li H . Lysine acetyltransferases and lysine deacetylases as targets for cardiovascular disease. Nat Rev Cardiol. 2019; 17(2):96-115. DOI: 10.1038/s41569-019-0235-9. View