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Updated: May 9, 2025
A Calcium Phosphate-Induced Mouse Abdominal Aortic Aneurysm Model
Published on: November 18, 2022
Calbindin 2 as a Novel Biomarker and Therapeutic Target for Abdominal Aortic Aneurysm: Integrative Analysis of Human
Yulin Bao1, Jiayi Chen1, Xudong Han1
1Department of Cardiology The First Affiliated Hospital with Nanjing Medical University Nanjing Jiangsu China.
Background:
Abdominal aortic aneurysm (AAA) is a clinical life-threatening issue. No pharmacological treatments are currently approved for the prevention and treatment of AAA. Therefore, identifying novel biomarkers and therapeutic targets is crucial for improving AAA management and outcomes.
Methods:
To identify plasma proteins with potential causal effects on AAA, we integrated genetic evidence from proteome-wide Mendelian randomization, genetic correlation, and colocalization analysis. The role of identified proteins in AAA was further explored through the phenome-wide association study and mediation analysis. Multiomics data analysis, including bulk RNA sequencing, single-cell/single-nucleus RNA sequencing, and spatial transcriptomics, was employed to characterize the expression patterns of these proteins. Experimental validation was performed using an AAA model in apolipoprotein E-deficient mice infused with angiotensin II. Druggability analysis was conducted to identify drug candidates, which were tested in preclinical mouse models.
Results:
CALB2 (calbindin 2) was identified as having a causal effect on AAA and may influence the progression of AAA through the regulation of lipid metabolism. Multiomics analysis revealed that CALB2 is predominantly expressed in the mesothelial cells of adipose tissues. Inhibition of CALB2 in an AAA mouse model alleviated AAA progression. Druggability analysis identified lenalidomide and genistein as potential therapeutic candidates, and experiments confirmed their efficacy in preventing AAA development.
Conclusions:
This study identifies CALB2 as being associated with an increased risk of AAA and suggests that i might be a novel biomarker and therapeutic molecule for AAA management. Lenalidomide and genistein hold promising potential as treatments for patients with AAA.
Insights
Calbindin 2 (CALB2) is a novel biomarker and therapeutic target for abdominal aortic aneurysm (AAA). Inhibiting CALB2 and using lenalidomide or genistein shows promise in preventing AAA development.
Area of Science:
- Genetics
- Proteomics
- Cardiovascular Research
Background:
- Abdominal aortic aneurysm (AAA) is a life-threatening condition with no approved pharmacological treatments.
- Identifying novel biomarkers and therapeutic targets is critical for improving AAA management and patient outcomes.
Purpose of the Study:
- To identify plasma proteins with potential causal effects on AAA using integrated genetic analyses.
- To explore the role of identified proteins in AAA pathogenesis and validate therapeutic targets.
Main Methods:
- Proteome-wide Mendelian randomization, genetic correlation, and colocalization analyses were used to identify causal proteins.
- Multiomics data (RNA sequencing, spatial transcriptomics) and phenome-wide association studies characterized protein expression and function.
- Experimental validation in an AAA mouse model and druggability analysis identified therapeutic candidates.
Main Results:
- Calbindin 2 (CALB2) was identified as a protein causally linked to AAA, potentially regulating lipid metabolism.
- CALB2 is primarily expressed in mesothelial cells of adipose tissue; its inhibition alleviated AAA progression in mice.
- Lenalidomide and genistein were identified as druggable candidates and showed efficacy in preventing AAA development in preclinical models.
Conclusions:
- CALB2 is a potential novel biomarker and therapeutic target for abdominal aortic aneurysm (AAA).
- Lenalidomide and genistein demonstrate promising therapeutic potential for AAA treatment.
