Zhenzhen Wang , Xiaoqiang Zhan , Shuai Yang , Yang Chen , Yingchao Bi , Xuemei Xian , Quangang Chen , Xufeng Han , Zhangping Yang , Renjin Chen
{"title":"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","authors":"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","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><p>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.</p></div><div><h3>Method and results</h3><p>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<sup>−/−</sup> mice. The adeno-associated viral (AAV) vectors expressing HO-2 was constructed, and the mice were received saline (ApoE<sup>−/−</sup>), AAV (ApoE<sup>−/−</sup>), AAV–HO–2 (ApoE<sup>−/−</sup>) 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<sup>−/−</sup> compared to control AAV-ApoE<sup>−/−</sup>.</p></div><div><h3>Conclusion</h3><p>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.</p></div>","PeriodicalId":10877,"journal":{"name":"Current Research in Pharmacology and Drug Discovery","volume":"4 ","pages":"Article 100141"},"PeriodicalIF":0.0000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9804009/pdf/","citationCount":"0","resultStr":"{\"title\":\"Heme-heme oxygenase-2 reduces the atherosclerosis by preventing inflammation\",\"authors\":\"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\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><p>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.</p></div><div><h3>Method and results</h3><p>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<sup>−/−</sup> mice. The adeno-associated viral (AAV) vectors expressing HO-2 was constructed, and the mice were received saline (ApoE<sup>−/−</sup>), AAV (ApoE<sup>−/−</sup>), AAV–HO–2 (ApoE<sup>−/−</sup>) 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<sup>−/−</sup> compared to control AAV-ApoE<sup>−/−</sup>.</p></div><div><h3>Conclusion</h3><p>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.</p></div>\",\"PeriodicalId\":10877,\"journal\":{\"name\":\"Current Research in Pharmacology and Drug Discovery\",\"volume\":\"4 \",\"pages\":\"Article 100141\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9804009/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current Research in Pharmacology and Drug Discovery\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S259025712200061X\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"Agricultural and Biological Sciences\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Research in Pharmacology and Drug Discovery","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S259025712200061X","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Agricultural and Biological Sciences","Score":null,"Total":0}
Heme-heme oxygenase-2 reduces the atherosclerosis by preventing inflammation
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.