Macrophage elastase derived from adventitial macrophages modulates aortic remodeling
Abdominal aortic aneurysm (AAA) is pathologically characterized by intimal atherosclerosis, disruption and attenuation of the elastic media, and adventitial inflammatory infiltrates. Although all these pathological events are possibly involved in the pathogenesis of AAA, the functional roles contrib...
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| Format: | Article |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.1097137/full |
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| author | Yajie Chen Yajie Chen Xiawen Yang Shuji Kitajima Longquan Quan Yao Wang Maobi Zhu Enqi Liu Liangxue Lai Liangxue Lai Haizhao Yan Haizhao Yan Haizhao Yan Jianglin Fan Jianglin Fan |
| author_facet | Yajie Chen Yajie Chen Xiawen Yang Shuji Kitajima Longquan Quan Yao Wang Maobi Zhu Enqi Liu Liangxue Lai Liangxue Lai Haizhao Yan Haizhao Yan Haizhao Yan Jianglin Fan Jianglin Fan |
| author_sort | Yajie Chen |
| collection | DOAJ |
| description | Abdominal aortic aneurysm (AAA) is pathologically characterized by intimal atherosclerosis, disruption and attenuation of the elastic media, and adventitial inflammatory infiltrates. Although all these pathological events are possibly involved in the pathogenesis of AAA, the functional roles contributed by adventitial inflammatory macrophages have not been fully documented. Recent studies have revealed that increased expression of matrix metalloproteinase-12 (MMP-12) derived from macrophages may be particularly important in the pathogenesis of both atherosclerosis and AAA. In the current study, we developed a carrageenan-induced abdominal aortic adventitial inflammatory model in hypercholesterolemic rabbits and evaluated the effect of adventitial macrophage accumulation on the aortic remodeling with special reference to the influence of increased expression of MMP-12. To accomplish this, we compared the carrageenan-induced aortic lesions of transgenic (Tg) rabbits that expressed high levels of MMP-12 in the macrophage lineage to those of non-Tg rabbits. We found that the aortic medial and adventitial lesions of Tg rabbits were greater in degree than those of non-Tg rabbits, with the increased infiltration of macrophages and prominent destruction of elastic lamellae accompanied by the frequent appearance of dilated lesions, while the intimal lesions were slightly increased. Enhanced aortic lesions in Tg rabbits were focally associated with increased dilation of the aortic lumens. RT-PCR and Western blotting revealed high levels of MMP-12 in the lesions of Tg rabbits that were accompanied by elevated levels of MMP-2 and -3, which was caused by increased number of macrophages. Our results suggest that adventitial inflammation constitutes a major stimulus to aortic remodeling and increased expression of MMP-12 secreted from adventitial macrophages plays an important role in the pathogenesis of vascular diseases such as AAA. |
| first_indexed | 2024-04-10T23:49:36Z |
| format | Article |
| id | doaj.art-ce5846235ef24baf8c5aeb1d3a5c0869 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-10T23:49:36Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-ce5846235ef24baf8c5aeb1d3a5c08692023-01-10T20:51:33ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-01-011010.3389/fcell.2022.10971371097137Macrophage elastase derived from adventitial macrophages modulates aortic remodelingYajie Chen0Yajie Chen1Xiawen Yang2Shuji Kitajima3Longquan Quan4Yao Wang5Maobi Zhu6Enqi Liu7Liangxue Lai8Liangxue Lai9Haizhao Yan10Haizhao Yan11Haizhao Yan12Jianglin Fan13Jianglin Fan14Guangdong Province Key Laboratory, Southern China Institute of Large Animal Models for Biomedicine, School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, ChinaDepartment of Molecular Pathology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi, JapanGuangdong Province Key Laboratory, Southern China Institute of Large Animal Models for Biomedicine, School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, ChinaAnalytical Research Center for Experimental Sciences, Saga University, Saga, JapanCollege of Animal Science and Technology, China Agricultural University, Beijing, ChinaGuangdong Province Key Laboratory, Southern China Institute of Large Animal Models for Biomedicine, School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, ChinaGuangdong Province Key Laboratory, Southern China Institute of Large Animal Models for Biomedicine, School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, ChinaResearch Institute of Atherosclerotic Disease and Laboratory Animal Center, Xi’an Jiaotong University School of Medicine, Xi’an, ChinaGuangdong Province Key Laboratory, Southern China Institute of Large Animal Models for Biomedicine, School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, ChinaKey Laboratory of Regenerative Biology, South China Institute for Stem Cell, Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong Province Key Laboratory, Southern China Institute of Large Animal Models for Biomedicine, School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, ChinaDepartment of Molecular Pathology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi, JapanKey Laboratory of Regenerative Biology, South China Institute for Stem Cell, Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, ChinaGuangdong Province Key Laboratory, Southern China Institute of Large Animal Models for Biomedicine, School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, ChinaDepartment of Molecular Pathology, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Yamanashi, JapanAbdominal aortic aneurysm (AAA) is pathologically characterized by intimal atherosclerosis, disruption and attenuation of the elastic media, and adventitial inflammatory infiltrates. Although all these pathological events are possibly involved in the pathogenesis of AAA, the functional roles contributed by adventitial inflammatory macrophages have not been fully documented. Recent studies have revealed that increased expression of matrix metalloproteinase-12 (MMP-12) derived from macrophages may be particularly important in the pathogenesis of both atherosclerosis and AAA. In the current study, we developed a carrageenan-induced abdominal aortic adventitial inflammatory model in hypercholesterolemic rabbits and evaluated the effect of adventitial macrophage accumulation on the aortic remodeling with special reference to the influence of increased expression of MMP-12. To accomplish this, we compared the carrageenan-induced aortic lesions of transgenic (Tg) rabbits that expressed high levels of MMP-12 in the macrophage lineage to those of non-Tg rabbits. We found that the aortic medial and adventitial lesions of Tg rabbits were greater in degree than those of non-Tg rabbits, with the increased infiltration of macrophages and prominent destruction of elastic lamellae accompanied by the frequent appearance of dilated lesions, while the intimal lesions were slightly increased. Enhanced aortic lesions in Tg rabbits were focally associated with increased dilation of the aortic lumens. RT-PCR and Western blotting revealed high levels of MMP-12 in the lesions of Tg rabbits that were accompanied by elevated levels of MMP-2 and -3, which was caused by increased number of macrophages. Our results suggest that adventitial inflammation constitutes a major stimulus to aortic remodeling and increased expression of MMP-12 secreted from adventitial macrophages plays an important role in the pathogenesis of vascular diseases such as AAA.https://www.frontiersin.org/articles/10.3389/fcell.2022.1097137/fullMMP-12macrophageelastinabdominal aortic aneurysmtransgenic rabbitsatherosclerosis |
| spellingShingle | Yajie Chen Yajie Chen Xiawen Yang Shuji Kitajima Longquan Quan Yao Wang Maobi Zhu Enqi Liu Liangxue Lai Liangxue Lai Haizhao Yan Haizhao Yan Haizhao Yan Jianglin Fan Jianglin Fan Macrophage elastase derived from adventitial macrophages modulates aortic remodeling Frontiers in Cell and Developmental Biology MMP-12 macrophage elastin abdominal aortic aneurysm transgenic rabbits atherosclerosis |
| title | Macrophage elastase derived from adventitial macrophages modulates aortic remodeling |
| title_full | Macrophage elastase derived from adventitial macrophages modulates aortic remodeling |
| title_fullStr | Macrophage elastase derived from adventitial macrophages modulates aortic remodeling |
| title_full_unstemmed | Macrophage elastase derived from adventitial macrophages modulates aortic remodeling |
| title_short | Macrophage elastase derived from adventitial macrophages modulates aortic remodeling |
| title_sort | macrophage elastase derived from adventitial macrophages modulates aortic remodeling |
| topic | MMP-12 macrophage elastin abdominal aortic aneurysm transgenic rabbits atherosclerosis |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.1097137/full |
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