HDAC2 counteracts vascular calcification by activating autophagy in chronic kidney disease

• Published in: The FASEB journal Vol. 38; no. 4; p. e23470
• Main Authors: Zhou, Guangyu, Liu, Pai, Zhang, Chen, Huang, Qun, Zhao, Zixia, Wu, Si, Li, Detian, Liu, Hongbo
• Format: Journal Article
• Language: English
• Published: United States 29.02.2024
• Subjects: HDAC2; chronic kidney disease; autophagy; vascular smooth muscle cells; vascular calcification
• ISSN: 1530-6860
• DOI: 10.1096/fj.202301429R

Vascular calcification is a major risk factor for cardiovascular disease mortality, with a significant prevalence in chronic kidney disease (CKD). Pharmacological inhibition of histone acetyltransferase has been proven to protect against from vascular calcification. However, the role of Histone Deacetylase 2 (HDAC2) and molecular mechanisms in vascular calcification of CKD remains unknown. An in vivo model of CKD was established using mouse fed with a high adenine and phosphate diet, and an in vitro model was produced using human aortic vascular smooth muscle cells (VSMCs) stimulated with β-glycerophosphate (β-GP). HDAC2 expression was found to be reduced in medial artery of CKD mice and β-GP-induced VSMCs. Overexpression of HDAC2 attenuated OPN and OCN upregulation, α-SMA and SM22α downregulation, and calcium deposition in aortas of CKD. The in vitro results also demonstrated that β-GP-induced osteogenic differentiation was inhibited by HDAC2. Furthermore, we found that HDAC2 overexpression caused an increase in LC3II/I, a decrease in p62, and an induction of autophagic flux. Inhibition of autophagy using its specific inhibitor 3-MA blocked HDAC2's protective effect on osteogenic differentiation in β-GP-treated VSMCs. Taken together, these results suggest that HDAC2 may protect against vascular calcification by the activation of autophagy, laying out a novel insight for the molecular mechanism in vascular calcification of CKD.