Cysteine and glycine-rich protein 3 (Crp3) as a critical regulator of elastolysis, inflammation, and smooth muscle cell apoptosis in abdominal aortic aneurysm development
Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease for which surgical or endovascular repair are the only currently available therapeutic strategies. The development of AAA involves the breakdown of elastic fibers (elastolysis), infiltration of inflammatory cells, and apoptosis o...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-12-01
|
| Series: | Frontiers in Physiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphys.2023.1252470/full |
| _version_ | 1797385981023748096 |
|---|---|
| author | Ana Barbosa Marcondes de Mattos Joao Carlos Ribeiro-Silva Miriam Helena Fonseca-Alaniz Iuri Cordeiro Valadão Erasmo Simão da Silva Jose Eduardo Krieger Ayumi Aurea Miyakawa |
| author_facet | Ana Barbosa Marcondes de Mattos Joao Carlos Ribeiro-Silva Miriam Helena Fonseca-Alaniz Iuri Cordeiro Valadão Erasmo Simão da Silva Jose Eduardo Krieger Ayumi Aurea Miyakawa |
| author_sort | Ana Barbosa Marcondes de Mattos |
| collection | DOAJ |
| description | Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease for which surgical or endovascular repair are the only currently available therapeutic strategies. The development of AAA involves the breakdown of elastic fibers (elastolysis), infiltration of inflammatory cells, and apoptosis of smooth muscle cells (SMCs). However, the specific regulators governing these responses remain unknown. We previously demonstrated that Cysteine and glycine-rich protein 3 (Crp3) sensitizes SMCs to apoptosis induced by stretching. Building upon this finding, we aimed to investigate the influence of Crp3 on elastolysis and apoptosis during AAA development. Using the elastase-CaCl2 rat model, we observed an increase in Crp3 expression, aortic diameter, and a reduction in wall thickness in wild type rats. In contrast, Crp3−/− rats exhibited a decreased incidence of AAA, with minimal or no changes in aortic diameter and thickness. Histopathological analysis revealed the absence of SMC apoptosis and degradation of elastic fibers in Crp3−/− rats, accompanied by reduced inflammation and diminished proteolytic capacity in Crp3−/− SMCs and bone marrow-derived macrophages. Collectively, our findings provide evidence that Crp3 plays a crucial role in AAA development by modulating elastolysis, inflammation, and SMC apoptosis. These results underscore the potential significance of Crp3 in the context of AAA progression and offer new insights into therapeutic targets for this disease. |
| first_indexed | 2024-03-08T22:02:16Z |
| format | Article |
| id | doaj.art-8f792ebf4dd146d384000868f704b23e |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-03-08T22:02:16Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-8f792ebf4dd146d384000868f704b23e2023-12-19T11:04:23ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2023-12-011410.3389/fphys.2023.12524701252470Cysteine and glycine-rich protein 3 (Crp3) as a critical regulator of elastolysis, inflammation, and smooth muscle cell apoptosis in abdominal aortic aneurysm developmentAna Barbosa Marcondes de Mattos0Joao Carlos Ribeiro-Silva1Miriam Helena Fonseca-Alaniz2Iuri Cordeiro Valadão3Erasmo Simão da Silva4Jose Eduardo Krieger5Ayumi Aurea Miyakawa6Laboratorio de Genética e Cardiologia Molecular, Instituto do Coração (InCor), Faculdade de Medicina da Universidade de São Paulo, São Paulo, BrazilLaboratorio de Genética e Cardiologia Molecular, Instituto do Coração (InCor), Faculdade de Medicina da Universidade de São Paulo, São Paulo, BrazilLaboratorio de Genética e Cardiologia Molecular, Instituto do Coração (InCor), Faculdade de Medicina da Universidade de São Paulo, São Paulo, BrazilLaboratorio de Genética e Cardiologia Molecular, Instituto do Coração (InCor), Faculdade de Medicina da Universidade de São Paulo, São Paulo, BrazilDivisão de Cirurgia Vascular e Endovascular, Departamento de Cirurgia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, BrazilLaboratorio de Genética e Cardiologia Molecular, Instituto do Coração (InCor), Faculdade de Medicina da Universidade de São Paulo, São Paulo, BrazilLaboratorio de Genética e Cardiologia Molecular, Instituto do Coração (InCor), Faculdade de Medicina da Universidade de São Paulo, São Paulo, BrazilAbdominal aortic aneurysm (AAA) is a life-threatening vascular disease for which surgical or endovascular repair are the only currently available therapeutic strategies. The development of AAA involves the breakdown of elastic fibers (elastolysis), infiltration of inflammatory cells, and apoptosis of smooth muscle cells (SMCs). However, the specific regulators governing these responses remain unknown. We previously demonstrated that Cysteine and glycine-rich protein 3 (Crp3) sensitizes SMCs to apoptosis induced by stretching. Building upon this finding, we aimed to investigate the influence of Crp3 on elastolysis and apoptosis during AAA development. Using the elastase-CaCl2 rat model, we observed an increase in Crp3 expression, aortic diameter, and a reduction in wall thickness in wild type rats. In contrast, Crp3−/− rats exhibited a decreased incidence of AAA, with minimal or no changes in aortic diameter and thickness. Histopathological analysis revealed the absence of SMC apoptosis and degradation of elastic fibers in Crp3−/− rats, accompanied by reduced inflammation and diminished proteolytic capacity in Crp3−/− SMCs and bone marrow-derived macrophages. Collectively, our findings provide evidence that Crp3 plays a crucial role in AAA development by modulating elastolysis, inflammation, and SMC apoptosis. These results underscore the potential significance of Crp3 in the context of AAA progression and offer new insights into therapeutic targets for this disease.https://www.frontiersin.org/articles/10.3389/fphys.2023.1252470/fullabdominal aortic aneurysmcysteine and glycine-rich protein-3smooth muscle cellapoptosiselastolysis |
| spellingShingle | Ana Barbosa Marcondes de Mattos Joao Carlos Ribeiro-Silva Miriam Helena Fonseca-Alaniz Iuri Cordeiro Valadão Erasmo Simão da Silva Jose Eduardo Krieger Ayumi Aurea Miyakawa Cysteine and glycine-rich protein 3 (Crp3) as a critical regulator of elastolysis, inflammation, and smooth muscle cell apoptosis in abdominal aortic aneurysm development Frontiers in Physiology abdominal aortic aneurysm cysteine and glycine-rich protein-3 smooth muscle cell apoptosis elastolysis |
| title | Cysteine and glycine-rich protein 3 (Crp3) as a critical regulator of elastolysis, inflammation, and smooth muscle cell apoptosis in abdominal aortic aneurysm development |
| title_full | Cysteine and glycine-rich protein 3 (Crp3) as a critical regulator of elastolysis, inflammation, and smooth muscle cell apoptosis in abdominal aortic aneurysm development |
| title_fullStr | Cysteine and glycine-rich protein 3 (Crp3) as a critical regulator of elastolysis, inflammation, and smooth muscle cell apoptosis in abdominal aortic aneurysm development |
| title_full_unstemmed | Cysteine and glycine-rich protein 3 (Crp3) as a critical regulator of elastolysis, inflammation, and smooth muscle cell apoptosis in abdominal aortic aneurysm development |
| title_short | Cysteine and glycine-rich protein 3 (Crp3) as a critical regulator of elastolysis, inflammation, and smooth muscle cell apoptosis in abdominal aortic aneurysm development |
| title_sort | cysteine and glycine rich protein 3 crp3 as a critical regulator of elastolysis inflammation and smooth muscle cell apoptosis in abdominal aortic aneurysm development |
| topic | abdominal aortic aneurysm cysteine and glycine-rich protein-3 smooth muscle cell apoptosis elastolysis |
| url | https://www.frontiersin.org/articles/10.3389/fphys.2023.1252470/full |
| work_keys_str_mv | AT anabarbosamarcondesdemattos cysteineandglycinerichprotein3crp3asacriticalregulatorofelastolysisinflammationandsmoothmusclecellapoptosisinabdominalaorticaneurysmdevelopment AT joaocarlosribeirosilva cysteineandglycinerichprotein3crp3asacriticalregulatorofelastolysisinflammationandsmoothmusclecellapoptosisinabdominalaorticaneurysmdevelopment AT miriamhelenafonsecaalaniz cysteineandglycinerichprotein3crp3asacriticalregulatorofelastolysisinflammationandsmoothmusclecellapoptosisinabdominalaorticaneurysmdevelopment AT iuricordeirovaladao cysteineandglycinerichprotein3crp3asacriticalregulatorofelastolysisinflammationandsmoothmusclecellapoptosisinabdominalaorticaneurysmdevelopment AT erasmosimaodasilva cysteineandglycinerichprotein3crp3asacriticalregulatorofelastolysisinflammationandsmoothmusclecellapoptosisinabdominalaorticaneurysmdevelopment AT joseeduardokrieger cysteineandglycinerichprotein3crp3asacriticalregulatorofelastolysisinflammationandsmoothmusclecellapoptosisinabdominalaorticaneurysmdevelopment AT ayumiaureamiyakawa cysteineandglycinerichprotein3crp3asacriticalregulatorofelastolysisinflammationandsmoothmusclecellapoptosisinabdominalaorticaneurysmdevelopment |