| Title: | Identification of the Hub Gene LDB3 in Stanford Type A Aortic Dissection Based on Comprehensive Bioinformatics Analysis |
| Journal: | Journal of Cellular and Molecular Medicine |
| Published: | 18 Mar 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40099963/ |
| DOI: | https://doi.org/10.1111/jcmm.70471 |
| URL: | https://onlinelibrary.wiley.com/doi/pdf/10.1111/jcmm.70471 |
Publication 16232
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
Stanford type A aortic dissection (TAAD) is a life-threatening disease. This study explored the role of LIM domain binding 3 (LDB3) in TAAD progression. Four datasets from the Gene Expression Omnibus were analyzed to identify TAAD-related hub genes. LDB3 single nucleotide polymorphisms (SNPs) were assessed in the UK Biobank. Western blotting and immunofluorescence detected LDB3 expression in angiotensin II (Ang II) stimulated human aortic vascular smooth muscle cells (HA-VSMC), human samples, and a murine model. Bioinformatics identified tissue inhibitor of metalloproteinase-1 (TIMP1) and LDB3 as TAAD hub genes. TIMP1 was expressed in macrophages, mesenchymal cells, and smooth muscle cells, while LDB3 was mostly expressed in smooth muscle cells. Validation showed TIMP1 was upregulated and LDB3 downregulated in TAAD. Six LDB3 SNPs were associated with aortic aneurysm and dissection in the UK Biobank. In human and murine samples, LDB3 expression was reduced in diseased tissues and co-localized with smooth muscle. Ang II-stimulated HA-VSMC exhibited LDB3 reduction and altered intercellular connections. The aforementioned findings suggest that the newly identified gene LDB3 is crucial in the progression of TAAD.</p>
16 Keywords
- Adaptor Proteins, Signal Transducing
- Angiotensin II
- Animals
- Aortic Dissection
- Computational Biology
- Disease Models, Animal
- Gene Expression Regulation
- Genetic Predisposition to Disease
- Humans
- LIM Domain Proteins
- Male
- Mice
- Muscle, Smooth, Vascular
- Myocytes, Smooth Muscle
- Polymorphism, Single Nucleotide
- Tissue Inhibitor of Metalloproteinase-1
9 Authors
- Xinyi Liu
- Xing Liu
- Bin Wan
- Yipeng Ge
- Haiou Hu
- Hong Yu
- Meng Zhao
- Huadong Li
- Junming Zhu
Enabling scientific discoveries that improve human health