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

Q2 Agricultural and Biological Sciences

Current Research in Pharmacology and Drug Discovery Pub Date : 2023-01-01 DOI:10.1016/j.crphar.2022.100141

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

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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.

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血红素-血红素加氧酶-2通过预防炎症来减少动脉粥样硬化

目的血红素加氧酶（HO）具有重要的抗氧化和抗炎特性，具有血管抗氧化作用。本研究旨在评估HO-2在动脉粥样硬化中的作用。方法和结果检测LPS和IL4诱导的M1和M2骨髓巨噬细胞中HO-2的表达水平。HO-2在M2巨噬细胞中的表达显著高于M1巨噬细胞。西方饮食（WD）导致ApoE−/-小鼠HO-2表达显著增加。构建表达HO-2的腺相关病毒（AAV）载体，并在12周时对小鼠进行生理盐水（ApoE−/-）、AAV（ApoE-−/-。结果显示，与对照组相比，AAV–HO–2具有较强的抵抗力，其表面主动脉、脂质水平、炎症细胞因子和M1巨噬细胞含量显著降低。结论巨噬细胞中HO-2的表达在抗动脉粥样硬化作用中起着重要作用，降低了动脉粥样硬化病变的炎症成分。这些结果表明HO-2可能是治疗心血管疾病的新靶点。

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