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ADAM17: A novel treatment target for aneurysms
Hualong Bai1, Liwei Zhang2, Peng Sun2
1Department of Vascular and Endovascular Surgery, First Affiliated Hospital of Zhengzhou University, Henan, China; Key Vascular Physiology and Applied Research Laboratory of Zhengzhou City, Henan, China.
Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|February 14, 2022
Summary
Inhibiting ADAM17 with TAPI-1 locally reduced abdominal aortic aneurysm (AAA) formation and progression in mouse and rat models. These findings highlight ADAM17 as a potential therapeutic target for AAA disease.
Area of Science:
- Vascular Biology
- Biomedical Engineering
- Pharmacology
Background:
- Abdominal aortic aneurysms (AAAs) pathogenesis remains incompletely understood.
- Previous research indicates elevated ADAM17 levels in aneurysmal tissue.
- ADAM17's role in AAA development requires further elucidation.
Purpose of the Study:
- To investigate the therapeutic potential of inhibiting ADAM17 in AAA formation and progression.
- To test the hypothesis that blocking ADAM17 activity can mitigate AAA development.
Main Methods:
- AAA models were created in mice (CaCl2-induced) and rats (pericardial patch angioplasty).
- ADAM17 inhibition was achieved using TAPI-1 delivered via hydrogel or coated patches.
- Immunofluorescence, bioinformatics, and immunostaining were employed for analysis.
Main Results:
- ADAM17 expression was significantly increased in mouse, rat, and human AAA tissues.
- Local delivery of TAPI-1 effectively reduced AAA formation and progression in both animal models.
- Bioinformatic and immunostaining analyses confirmed ADAM17's role in promoting M1 macrophage and vascular smooth muscle cell transformation.
Conclusions:
- Local administration of an ADAM17 inhibitor demonstrated efficacy in preventing AAA development.
- These findings establish ADAM17 as a critical factor in AAA pathogenesis.
- ADAM17 inhibition presents a promising therapeutic strategy for treating abdominal aortic aneurysms.
