Heme-heme oxygenase-2 reduces the atherosclerosis by preventing inflammation

Zhenzhen Wang; Xiaoqiang Zhan; Shuai Yang; Yang Chen; Yingchao Bi; Xuemei Xian; Quangang Chen; Xufeng Han; Zhangping Yang; Renjin Chen

doi:10.1016/j.crphar.2022.100141

Heme-heme oxygenase-2 reduces the atherosclerosis by preventing inflammation

Curr Res Pharmacol Drug Discov. 2022 Dec 12:4:100141. doi: 10.1016/j.crphar.2022.100141. eCollection 2023.

Authors

Zhenzhen Wang¹, Xiaoqiang Zhan², Shuai Yang², Yang Chen², Yingchao Bi², Xuemei Xian², Quangang Chen², Xufeng Han², Zhangping Yang³, Renjin Chen^{2

3}

Affiliations

¹ Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
² College of Life Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, China.
³ Jiangsu Key Laboratory of Animal Genetic Breeding and Molecular Design, Yangzhou University, Yangzhou, Jiangsu, China.

Abstract

Objective: Heme oxygenase (HO) has been shown to have important antioxidant and anti-inflammatory properties, resulting in a vascular antitherogenic effect. This study was undertaken to evaluate the role of HO-2 in atherosclerosis.

Method and results: The expression levels of HO-2 were evaluated in M1 and M2 bone marrow macrophage induced by LPS and IL4. The expression of HO-2 was significantly higher in M2 macrophage than in M1 macrophage. Western diet (WD) caused a significant increase in HO-2 expression in ApoE^-/- mice. The adeno-associated viral (AAV) vectors expressing HO-2 was constructed, and the mice were received saline (ApoE^-/-), AAV (ApoE^-/-), AAV-HO-2 (ApoE^-/-) on WD at 12 weeks and their plasma lipids, inﬂammatory cytokines, atherosclerosis were evaluated for 16 weeks. The results showed AAV-HO-2 was robust, with a significant decrease in the en face aortas, lipids levels, inﬂammatory cytokines and M1 macrophage content in AAV-HO-2 ApoE^-/- compared to control AAV-ApoE^-/-.

Conclusion: HO-2 expression in macrophages plays an important role of the antiatherogenic effect, decreasing the inflammatory component of atherosclerotic lesions. These results suggest that HO-2 may be a novel therapeutic target for cardiovascular diseases.

Keywords: Atherosclerosis; Heme oxygenase-2; Inflammation; Macrophages.