Overexpression of CuZn superoxide dismutase improves high-density lipoprotein function in swine

Lichun Zhang; Tianliang Zhang; Xiaofeng Chen; Fengjiao Wang; Li Liu; Yanmei Yang; Yongqing Zeng; Yanhong Si; Nana Yang

doi:10.1016/j.prostaglandins.2024.106817

Overexpression of CuZn superoxide dismutase improves high-density lipoprotein function in swine

Prostaglandins Other Lipid Mediat. 2024 Feb 6:172:106817. doi: 10.1016/j.prostaglandins.2024.106817. Online ahead of print.

Authors

Lichun Zhang¹, Tianliang Zhang², Xiaofeng Chen³, Fengjiao Wang⁴, Li Liu¹, Yanmei Yang¹, Yongqing Zeng⁵, Yanhong Si⁶, Nana Yang⁷

Affiliations

¹ Medical Laboratory Animal Center, School of Life Science and Technology, Weifang Medical University, Weifang, Shandong, China.
² Experimental Center for Medical Research, Weifang Medical University, Weifang, Shandong, China.
³ Beijing Chest Hospital, Capital Medical University, Beijing, China.
⁴ Medical Laboratory Animal Center, School of Public Health, Weifang Medical University, Weifang, Shandong, China.
⁵ Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, College of Animal Science and Technology, Shandong Agricultural University, Taian, Shandong, China. Electronic address: yqzeng@sdau.edu.cn.
⁶ Basic Medical College, Shandong First Medical University, Taian, Shandong, China. Electronic address: zhaosixinkang@163.com.
⁷ Medical Laboratory Animal Center, School of Life Science and Technology, Weifang Medical University, Weifang, Shandong, China; Weifang Key Laboratory of Animal Model Research on Cardiovascular and Cerebrovascular Diseases, Weifang, Shandong, China. Electronic address: benben1980@126.com.

PMID: 38331090
DOI: 10.1016/j.prostaglandins.2024.106817

Abstract

Cardiovascular disease (CVD) has been the leading cause of death worldwide. As a chronic inflammatory disease, atherosclerosis (AS) acts as the initiating factor for CVD and reactive oxygen species (ROS) play a vital role in its development. Superoxide dismutases (SOD) can alleviate the detrimental effects of ROS and serve as the first line of defense through detoxifying the products derived from oxidative stress in vivo. Considering the potential preventive effects of high-density lipoprotein (HDL) on AS and the close relationship between CuZn superoxide dismutase (CuZnSOD) and HDL, the present work investigated whether CuZnSOD overexpression in swine could improve the function of HDL. Seven CuZnSOD transgenic swine, constructed by sperm and magnetic nanoparticles, demonstrated overexpressed CuZnSOD in the liver (P < 0.01) but comparable level to control in plasma (P > 0.05). CuZnSOD overexpression significantly down-regulated the levels of triglyceride (TG), apolipoprotein A-I (apoA-I) (P < 0.05), and high-density lipoprotein cholesterol (HDL-C) (P < 0.01) in plasma. In the presence of CuZnSOD overexpression, HDL3 significantly inhibited levels of IL-6 and TNF-α induced by oxidized low-density lipoprotein (oxLDL) (P < 0.05), indicating enhanced anti-inflammatory activity of HDL. At the same time, HDL-mediated cholesterol efflux did not decrease (P > 0.05). CuZnSOD overexpression improves the anti-inflammatory function of HDL despite decreased levels of HDL-C. In Conclusion, CuZnSOD overexpression improves HDL function in swine.

Keywords: Atherosclerosis; Cardiovascular disease; Cholesterol efflux; CuZn superoxide dismutase; High-density lipoprotein.