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  3. Sirt7 protects against vascular calcification via modulation of reactive oxygen species and senescence of vascular smooth muscle cells

Sirt7 protects against vascular calcification via modulation of reactive oxygen species and senescence of vascular smooth muscle cells

  • Free Radic Biol Med. 2024 Jul 23:223:30-41. doi: 10.1016/j.freeradbiomed.2024.07.021.
Hongjiao Yu 1,  Yuchen Xie 2,  Lan Lan 3,  Siyu Ma 4,  Simon Wing Fai Mok 5,  Io Nam Wong 5,  Yueheng Wang 2,  Guoli Zhong 2,  Liang Yuan 2,  Huan Zhao 2,  Xiao Hu 6,  Vicky E Macrae 7,  Shengping He 8,  Guojun Chen 9,  Dongxing Zhu 10
Affiliations

Affiliations

  • 1 Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510260, China; GMU-GIBH Joint School of Life Sciences, The Guangdong-Hong Kong-Macao Joint Laboratory for Cell Fate Regulation and Diseases, Guangzhou Medical University, China.
  • 2 Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, 510260, China.
  • 3 Department of Anesthesiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
  • 4 GMU-GIBH Joint School of Life Sciences, The Guangdong-Hong Kong-Macao Joint Laboratory for Cell Fate Regulation and Diseases, Guangzhou Medical University, China.
  • 5 Faculty of Medicine, Macau University of Science and Technology, Taipa, Macau, China.
  • 6 Department of Cardiology, Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • 7 Functional Genetics and Development, The Royal (Dick) School of Veterinary Studies and the Roslin Institute, University of Edinburgh, Midlothian, UK.
  • 8 Department of Cardiovascular Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, Guangdong, 510515, China. Electronic address: hsp@smu.edu.cn.
  • 9 Department of Cardiology, Guangdong Provincial Key Laboratory of Cardiac Function and Microcirculation, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China. Electronic address: chenguojun@i.smu.edu.cn.
  • 10 Guangzhou Institute of Cardiovascular Disease, Guangdong Key Laboratory of Vascular Diseases, State Key Laboratory of Respiratory Disease, The Second Affiliated Hospital, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong, 510260, China. Electronic address: dongxing.zhu@gzhmu.edu.cn.
PMID: 39053861 DOI: 10.1016/j.freeradbiomed.2024.07.021
Abstract

Vascular calcification is frequently seen in patients with chronic kidney disease (CKD), and significantly increases cardiovascular mortality and morbidity. SIRT7, a NAD+-dependent histone deacetylases, plays a crucial role in Cardiovascular Disease. However, the role of SIRT7 in vascular calcification remains largely unknown. Using in vitro and in vivo models of vascular calcification, this study showed that SIRT7 expression was significantly reduced in calcified arteries from mice administered with high dose of vitamin D3 (vD3). We found that knockdown or inhibition of SIRT7 promoted vascular smooth muscle cell (VSMC), aortic ring and vascular calcification in mice, whereas overexpression of SIRT7 had opposite effects. Intriguingly, this protective effect of SIRT7 on vascular calcification is dependent on its deacetylase activity. Unexpectedly, SIRT7 did not alter the osteogenic transition of VSMCs. However, our RNA-seq and subsequent studies demonstrated that knockdown of SIRT7 in VSMCs resulted in increased intracellular Reactive Oxygen Species (ROS) accumulation, and induced an Nrf-2 mediated oxidative stress response. Treatment with the ROS inhibitor N-acetylcysteine (NAC) significantly attenuated the inhibitory effect of SIRT7 on VSMC calcification. Furthermore, we found that knockdown of SIRT7 delayed cell cycle progression and accelerated cellular senescence of VSMCs. Taken together, our results indicate that SIRT7 regulates vascular calcification at least in part through modulation of ROS and cellular senescence of VSMCs. SIRT7 may be a potential therapeutic target for vascular calcification.

Keywords

Cellular senescence; Reactive oxygen species; Sirt7; Vascular calcification.

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