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Updated: May 8, 2025
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Hydrogel Nanoparticle Harvesting of Plasma or Urine for Detecting Low Abundance Proteins
Published on: August 7, 2014
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A Novel Hidden Protein p-414aa Encoded by circSETD2(14,15) Inhibits Vascular Remodeling
Si-Fan Wang1,2, Li-Yun Yang1, An-Qi Zhao1
1Department of Biochemistry and Molecular Biology, Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Key Laboratory of Forensic Medicine, Hebei Medical University, Shijiazhuang, China (S.-F.W., L.-Y.Y., A.-Q.Z., Z.-Y.W., S.W., M.G., S.-G.S.).
Circulation
|March 18, 2025
Summary
A novel protein, p-414aa, derived from circSETD2(14,15) inhibits vascular smooth muscle cell proliferation and neointimal hyperplasia. This discovery offers potential new therapeutic targets for vascular remodeling diseases like atherosclerosis and hypertension.
Area of Science:
- Vascular Biology
- Molecular Biology
- Genetics
Background:
- Vascular smooth muscle cell (VSMC) phenotypic switching drives neointimal hyperplasia, a key process in vascular remodeling diseases.
- Circular RNAs (circRNAs) encode novel proteins, but their role in vascular remodeling remains largely unexplored.
- This study investigates a circRNA-derived protein's function in VSMC regulation.
Purpose of the Study:
- To identify and characterize novel proteins encoded by circRNAs in VSMCs.
- To elucidate the mechanism by which a specific circRNA-derived protein impacts VSMC proliferation and vascular remodeling.
- To assess the therapeutic potential of this novel protein in vascular diseases.
Main Methods:
- VSMC proliferation assays were conducted to evaluate the effects of circSETD2(14,15).
- Techniques including vector construction, immunoprecipitation-mass spectrometry, and dual-luciferase reporter assays confirmed the novel protein p-414aa.
- Interactions between p-414aa, HuR, and C-FOS mRNA were validated using co-immunoprecipitation, mass spectrometry, proximity ligation assay, RNA sequencing, and RNA immunoprecipitation.
- A carotid artery ligation model in male mice was used to assess the role of p-414aa in neointimal hyperplasia.
Main Results:
- Overexpression of circSETD2(14,15) was found to inhibit VSMC phenotypic switching.
- The novel protein p-414aa, encoded by circSETD2(14,15), interacts with HuR.
- This interaction reduces C-FOS mRNA stability, suppressing VSMC proliferation and neointimal hyperplasia in vivo.
Conclusions:
- A novel circRNA-derived protein, p-414aa, inhibits vascular remodeling by modulating VSMC proliferation.
- CircSETD2(14,15) and its encoded protein p-414aa represent potential therapeutic targets for vascular remodeling diseases.
- This study reveals a new mechanism involving circRNA-derived proteins in vascular health and disease.
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