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A Mouse Abdominal Aortic Aneurysm Model by Periadventitial Calcium Chloride and Elastase Infiltration
Published on: August 2, 2024
Do cathepsins play a role in abdominal aortic aneurysm pathogenesis?
Galina K Sukhova1, Guo-Ping Shi
1Division of Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, NRB-7, Room 730J, Boston, MA 02115, USA. gsukhova@rics.bwh.harvard.edu
Annals of the New York Academy of Sciences
|December 22, 2006
Summary
Cysteine proteases, like cathepsins, play a key role in atherosclerosis and abdominal aortic aneurysm (AAA) development. Their imbalance with inhibitors like cystatin C disrupts arterial integrity, impacting vascular diseases.
Area of Science:
- Vascular Biology
- Biochemistry
- Pathology
Background:
- Cysteine proteases, particularly cathepsins S and K, have been implicated in atherosclerosis and abdominal aortic aneurysm (AAA) formation.
- These enzymes, especially cathepsins, exhibit potent elastolytic activity, suggesting a significant role in aneurysm development.
- Their activity in human atherosclerotic and aneurysmal lesions has been demonstrated.
Purpose of the Study:
- To investigate the role of cysteine proteases and their inhibitors in the pathogenesis of atherosclerosis and AAA.
- To explore the relationship between cathepsins and cystatin C levels in aneurysmal tissue.
- To summarize evidence from human studies and animal models regarding cathepsin involvement in vascular diseases.
Main Methods:
- Analysis of cathepsin and cystatin C presence and activity in human atherosclerotic and aneurysmal lesions.
- In vitro studies with different cell types.
- In vivo studies using genetically modified mice lacking specific cathepsins or cystatin C.
Main Results:
- Overexpression of elastolytic cathepsins and suppression of cystatin C were observed in aneurysmal tissue.
- Cathepsins were implicated in microvessel formation and apoptosis, processes relevant to AAA.
- Mice lacking cathepsins showed reduced atherosclerosis and AAA, while cystatin C deficiency exacerbated AAA features in ApoE-null mice.
Conclusions:
- The balance between cysteine proteases and protease inhibitors is crucial for maintaining arterial integrity.
- Dysregulation of this balance contributes to arterial remodeling in atherosclerosis and AAA.
- Cysteine proteases are key players in the development and progression of vascular diseases like AAA.
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