The role and mechanism of the zinc finger gene ZNF580 in foam cell formation

Article type: Research Article

Authors: Zhang, Zhongbai^a | Qin, Xueting^b | Chen, Jingxun^c | Li, Yanchun^d | Chen, Huaxin^e | Xie, Hongwei^f | Yang, Min^g | Li, Chuang^h | Wang, Zhenghuiⁱ | Zhang, Mei^{h; *}

Affiliations: [a] The Fourth Detachment, China Coast Guard, Wenchang, Hainan, China | [b] Department of Nephrology with Integrated Traditional Chinese and Western Medicine, The Second People’s Hospital of Yichang, Yichang, Hubei, China | [c] Faculty of Biomedical Engineering, The Chinese University of Hong Kong, Hongkong, China | [d] Department of Pharmacy,Heilongjiang Municipal Corps Hospital of Chinese people’s Armed Police Force, Harbin, Heilongjiang, China | [e] Department of Anesthesia, Hainan Hospital of PLA General Hospital, Sanya, Hainan, China | [f] Department of Health Service, Logistics University of People’s Armed Police Force, Tianjin, China | [g] Department of Psychology, Heilongjiang Municipal Corps Hospital of Chinese People’s Armed Police Force, Harbin, Heilongjiang, China | [h] Department of Cardiac Thoracic Surgery, Characteristic Medical Center of People’s Armed Police Force, Tianjin, China | [i] Department of Human Morphology Section, Logistics University of People’s Armed Police Force, Tianjin, China

Correspondence: [*] Corresponding author: Mei Zhang, Department of Cardiac Thoracic Surgery, Characteristic Medical Center of People’s Armed Police Force, Tianjin 300309. E-mail:[email protected].

Abstract: Coronary atherosclerotic heart disease is an important threat to human health. The pathological basis is atherosclerosis, and foam cell formation is the key link in the initiation of atherosclerosis. Here, foam cell models were established using 50 ng/ml oxidized low-density lipoprotein (ox-LDL) to stimulate in vitro cultures of THP-1 cells for 72 h. The expression of ZNF580, a Cys2–His2 (C2H2) zinc finger protein containing 172 amino acids that was originally cloned by screening a human aortic cDNA library, was measured in foam cells, and its interaction with various regulatory factors during foam cell formation was investigated. Oil red O (ORO) staining was used to observe cell morphology and intracellular lipid levels. Lentivirus transfection was used to induce high ZNF580 expression (Ad-ZNF580) and low ZNF580 expression (Si-ZNF580) in THP-1 cells, and a fluorescent inverted microscope was used to observe the distribution of ZNF580 immunofluorescence to deduce the transfection rate. RNA and total protein were extracted, and the expression levels of ZNF580, cluster of differentiation 36 (CD36), peroxisome proliferator activated receptor-γ (PPAR-γ), ATP-binding cassette transporter A1 (ABCA1) and apolipoprotein E (ApoE) were measured by real-time quantitative PCR. The protein levels were examined by western blotting to evaluate the interaction between ZNF580 and associated regulatory factors. ZNF580 can significantly increase the expression levels of ApoE and ABCA1 and significantly decrease the expression levels of CD36 and PPAR-γ, suggesting that ZNF580-mediated inhibition of foam cell formation is associated with the PPAR-γ-CD36 signalling pathway. Based on these findings, ZNF580 might be a potential therapeutic candidate for the treatment of coronary atherosclerotic heart disease.

Keywords: ZNF 580, cardiovascular disease, atherosclerosis, foam cells

DOI: 10.3233/JCB-220063

Journal: Journal of Cellular Biotechnology, vol. 10, no. 1, pp. 1-15, 2024