J Cardiovasc Interv.  2024 Jul;3(3):158-176. 10.54912/jci.2024.0011.

The Role of Class I and IIa Histone Deacetylases in Atherosclerosis and Vascular Calcification

• Kee HJ
• Kim SH
• Jeong SM
• Sim DS
• Hong YJ
• Jeong MH

• KMID: 2561213
• DOI: http://doi.org/10.54912/jci.2024.0011

Abstract

Histone deacetylases (HDACs) are enzymes that remove the acetyl group of histone and non-histone proteins that are susceptible to post-translational modifications, such as phosphorylation, by a variety of stimuli. Unlike class I HDACs (HDAC1, 2, 3, and 8), class IIa HDACs (HDAC4, 5, 7, and 9) accumulate in the cytoplasm when phosphorylated and have opposite effects when present in the nucleus. Atherosclerosis is a condition caused by fatty deposits on blood vessel walls, which, when advanced, leads to calcified lesions. HDACs play different roles in vascular endothelial cell dysfunction, vessel wall remodeling, inflammation, plaque formation and stability, and vascular calcification. In vascular endothelial cell dysfunction, plaque destruction, and calcification, HDACs have mixed aggravating and protective effects. In vascular smooth muscle cell proliferation and foam cell formation, most HDACs (except HDAC7u) promote these processes. The most promising targets for vascular calcification treatment are HDAC4, HDAC8, and HDAC9. In this review, we discuss class I and class IIa HDACs and suggest potential therapeutic targets for atherosclerosis and calcification.

Keyword

Histone deacetylases; Post-translational modification; Atherosclerosis; Vascular calcification