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Cysteine and glycine-rich protein 3 (Crp3) as a critical regulator of elastolysis, inflammation, and smooth muscle cell apoptosis in abdominal aortic aneurysm development

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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
Authors: 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
Source: Frontiers in Physiology, Vol 14 (2023)
Publisher Information: Frontiers Media S.A., 2023.
Publication Year: 2023
Collection: LCC:Physiology
Subject Terms: abdominal aortic aneurysm, cysteine and glycine-rich protein-3, smooth muscle cell, apoptosis, elastolysis, Physiology, QP1-981
More Details: 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.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1664-042X
Relation: https://www.frontiersin.org/articles/10.3389/fphys.2023.1252470/full; https://doaj.org/toc/1664-042X
DOI: 10.3389/fphys.2023.1252470
Access URL: https://doaj.org/article/8f792ebf4dd146d384000868f704b23e
Accession Number: edsdoj.8f792ebf4dd146d384000868f704b23e
Database: Directory of Open Access Journals
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  Data: Cysteine and glycine-rich protein 3 (Crp3) as a critical regulator of elastolysis, inflammation, and smooth muscle cell apoptosis in abdominal aortic aneurysm development
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  Data: <searchLink fieldCode="AR" term="%22Ana+Barbosa+Marcondes+de+Mattos%22">Ana Barbosa Marcondes de Mattos</searchLink><br /><searchLink fieldCode="AR" term="%22Joao+Carlos+Ribeiro-Silva%22">Joao Carlos Ribeiro-Silva</searchLink><br /><searchLink fieldCode="AR" term="%22Miriam+Helena+Fonseca-Alaniz%22">Miriam Helena Fonseca-Alaniz</searchLink><br /><searchLink fieldCode="AR" term="%22Iuri+Cordeiro+Valadão%22">Iuri Cordeiro Valadão</searchLink><br /><searchLink fieldCode="AR" term="%22Erasmo+Simão+da+Silva%22">Erasmo Simão da Silva</searchLink><br /><searchLink fieldCode="AR" term="%22Jose+Eduardo+Krieger%22">Jose Eduardo Krieger</searchLink><br /><searchLink fieldCode="AR" term="%22Ayumi+Aurea+Miyakawa%22">Ayumi Aurea Miyakawa</searchLink>
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  Data: 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.
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      – Text: English
    Subjects:
      – SubjectFull: abdominal aortic aneurysm
        Type: general
      – SubjectFull: cysteine and glycine-rich protein-3
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