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Updated: Sep 18, 2025
08:28
Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro
Published on: February 15, 2022
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FAM49B Fragmentation by Asparagine Endopeptidase Promotes Vascular Smooth Muscle Cell Migration in Atherogenesis
Xuying Xiang1, Mengting Qin1, Lei Nie1
1Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China (X.X., M.Q., L.N., X.G., J.C., D.J., L.M.).
Arteriosclerosis, Thrombosis, and Vascular Biology
|June 26, 2025
Summary
FAM49B fragments promote vascular smooth muscle cell migration and atherosclerosis. Inhibiting asparagine endopeptidase (AEP) cleavage of FAM49B may offer a therapeutic strategy for atherosclerosis.
Area of Science:
- Cardiovascular Biology
- Molecular Mechanisms of Atherosclerosis
Background:
- Vascular smooth muscle cell (VSMC) migration is crucial in atherosclerosis development, but underlying molecular pathways remain unclear.
- FAM49B (family with sequence similarity 49 member B) fragments were detected in atherosclerotic plaques, prompting investigation into their role.
Purpose of the Study:
- To elucidate the role of FAM49B fragments in VSMC migration and atherogenesis.
- To investigate the mechanism by which FAM49B fragments influence atherosclerosis progression.
Main Methods:
- Utilized transgenic mouse models (Aep-/- , Aep-/- Apoe-/- , and VSMC-specific FAM49B overexpression).
- Employed adenovirus gene transfer for FAM49B fragment overexpression and analyzed the effects of an AEP inhibitor (compound 11).
- Identified FAM49B fragments via mass spectrometry and analyzed their expression in atherosclerotic plaques using immunofluorescence and immunoblotting.
Main Results:
- FAM49B fragments, generated by AEP cleavage, are upregulated in atherosclerotic lesions and VSMCs.
- FAM49B fragments, unlike full-length FAM49B, promote VSMC migration by activating Rac1 and inducing actin polymerization.
- Overexpression of FAM49B fragments increased atherosclerotic burden in mice, while AEP deletion or AEP inhibition reduced plaque size.
Conclusions:
- AEP-derived FAM49B fragments enhance Rac1-mediated VSMC migration, thereby promoting atherosclerosis.
- Targeting AEP-mediated FAM49B fragmentation presents a potential therapeutic strategy for atherosclerosis.
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