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Updated: Sep 12, 2025
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Quantitative Micro-CT Analysis of Aortopathy in a Mouse Model of β-aminopropionitrile-induced Aortic Aneurysm and Dissection
Published on: July 16, 2018
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Copy number loss Of APP cause thoracic aortic dissection
Qiannan Gao1,2, Minghui Bao3, Jiangshan Tan2
1Beijing Anzhen Hospital of Capital Medical University and Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China.
Summary
Copy number variations in APP accelerate thoracic aortic dissection (TAD) progression. APP deficiency exacerbates aortic damage and promotes TAD, highlighting APP as a potential therapeutic target and genetic risk factor for this deadly condition.
Area of Science:
- Cardiovascular Research
- Genetics
- Molecular Biology
Background:
- Thoracic aortic dissection (TAD) is a major cause of sudden cardiovascular death.
- Limited research exists on copy number variations (CNVs) in sporadic TAD, necessitating large-scale studies.
Purpose of the Study:
- To comprehensively investigate and functionally validate CNVs in sporadic TAD using whole genome sequencing (WGS).
- To elucidate the role of identified genes in TAD pathogenesis in vivo and in vitro.
Main Methods:
- Whole genome sequencing (WGS) in 257 sporadic TAD patients and 132 controls.
- Gene knockout mice models and in vitro experiments (RNA-seq, molecular biology).
- Analysis of CNVs, gene expression, and cellular mechanisms in TAD.
Main Results:
- Identified four potential CNV genes (DSCAM, APP, LINC00907, PROCR) in TAD.
- Reduced APP expression observed in TAD patients' aortas.
- APP deficiency exacerbated elastic fiber fragmentation and promoted TAD formation in mouse models, inducing VSMC apoptosis and secretory phenotype switch in vitro.
Conclusions:
- This study is the first to report novel CNVs of APP in TAD.
- APP deficiency accelerates TAD initiation and progression.
- APP is a promising therapeutic target and potential genetic risk factor for TAD.
Keywords:
APPAortic dissectionCopy number variantsVascular smooth muscle cell.Whole genome sequencingMore Related Videos
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