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Updated: Jan 20, 2026
Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
Semaphorin 7A aggravates abdominal aortic aneurysm through PDK1/SGK3/YTHDC1 axis-mediated phenotypic switching of
Fengchan Li1,2, Zhen Zhu1, Fan Tang1
1Cyrus Tang Medical Institute, Soochow University, Suzhou, China.
Aims:
Semaphorin 7A (SEMA7A), a membrane-anchored glycoprotein involved in immune and vascular signalling, has been implicated in cardiovascular diseases. However, its role in the development of abdominal aortic aneurysm (AAA) has not been defined. In this study, we investigated the role of SEMA7A in AAA progression and the underlying mechanisms.
Methods And Results:
A meta-analysis of genome-wide association studies identified SEMA7A as a candidate gene involved in AAA formation. Global and vascular smooth muscle cell (VSMC)-specific Sema7a knockout mice were generated and subjected to a CaPO4-induced AAA model. Compared with wild-type controls, SEMA7A-deficient mice exhibited a 28.6% reduction in aortic expansion, a finding that was recapitulated in VSMC-specific Sema7a knockout mice. RNA sequencing of CaPO4-stimulated mouse VSMCs, along with immunofluorescence staining of AAA tissues, revealed that SEMA7A deficiency suppressed VSMC phenotypic switching. Further mechanistic studies demonstrated that SEMA7A promotes this switching via the integrin α5β1-mediated PDK1/SGK3/YTHDC1 signalling axis. Notably, administration of a synthetic SEMA7A-mimicking small peptide, ACP, significantly inhibited VSMC phenotypic switching and attenuated AAA progression.
Conclusion:
This study underscores the critical role of SEMA7A in regulating VSMC phenotypic switching through a novel PDK1/SGK3/YTHDC1 axis, which contributes to AAA pathogenesis, suggesting that targeting SEMA7A is a promising therapeutic strategy for AAA prevention and treatment.
Insights
Semaphorin 7A (SEMA7A) is critical in abdominal aortic aneurysm (AAA) development by promoting vascular smooth muscle cell (VSMC) switching. Inhibiting SEMA7A shows promise for preventing and treating AAA.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Vascular Biology
Background:
- Semaphorin 7A (SEMA7A) is a glycoprotein involved in immune and vascular signaling, implicated in cardiovascular diseases.
- The specific role of SEMA7A in abdominal aortic aneurysm (AAA) pathogenesis remains undefined.
Purpose of the Study:
- To investigate the role of SEMA7A in AAA progression.
- To elucidate the underlying molecular mechanisms of SEMA7A in AAA development.
Main Methods:
- Genome-wide association studies (GWASs) meta-analysis identified SEMA7A as a candidate gene.
- Generation and analysis of global and vascular smooth muscle cell (VSMC)-specific Sema7a knockout mice in a CaPO4-induced AAA model.
- RNA sequencing of VSMCs and immunofluorescence staining of AAA tissues were performed.
Main Results:
- SEMA7A deficiency in mice reduced aortic expansion by 28.6%, confirmed in VSMC-specific knockout models.
- SEMA7A suppression inhibited VSMC phenotypic switching, a key process in AAA.
- Mechanistic studies revealed SEMA7A promotes VSMC switching via the integrin α5β1-mediated PDK1/SGK3/YTHDC1 signaling axis.
- A SEMA7A-mimicking peptide (ACP) inhibited VSMC switching and attenuated AAA progression.
Conclusions:
- SEMA7A critically regulates VSMC phenotypic switching through the novel PDK1/SGK3/YTHDC1 axis.
- This pathway contributes significantly to AAA pathogenesis.
- Targeting SEMA7A represents a promising therapeutic strategy for AAA prevention and treatment.
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