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

• Published in: Frontiers in physiology Vol. 14; p. 1252470
• Main Authors: de Mattos, Ana Barbosa Marcondes, Ribeiro-Silva, Joao Carlos, Fonseca-Alaniz, Miriam Helena, Valadão, Iuri Cordeiro, da Silva, Erasmo Simão, Krieger, Jose Eduardo, Miyakawa, Ayumi Aurea
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 19-12-2023
• Subjects: abdominal aortic aneurysm; apoptosis; cysteine and glycine-rich protein-3; elastolysis; Physiology; smooth muscle cell; apoptosis; smooth muscle cell; cysteine and glycine-rich protein-3; abdominal aortic aneurysm; elastolysis
• ISSN: 1664-042X; 1664-042X
• DOI: 10.3389/fphys.2023.1252470

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-CaCl
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.