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Updated: Sep 18, 2025

Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro
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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
PubMed
Abstract

Insights

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.
Keywords:
actinatherosclerosiscell movementcysteine proteasemyocytes, smooth musclepseudopodia

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