Related Experiment Video
Updated: Jan 18, 2026
Measurement of Pulse Propagation Velocity, Distensibility and Strain in an Abdominal Aortic Aneurysm Mouse Model
Published on: February 23, 2020
UCP2 is identified as a therapeutic target for abdominal aortic aneurysm by comprehensive bioinformatic analysis and
Maohua Li1, Shasha Xiao2, Qi Qin2
1Department of Vascular Surgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, China; Molecular Biology Research Center, School of Life Sciences, Hunan Province Key Laboratory of Basic and Applied Hematology, Central South University, Changsha, 410013, China.
Abstract:
Abdominal aortic aneurysm (AAA) is a potentially life-threatening vascular condition that currently lacks effective pharmacological treatment. The disease is strongly associated with chronic inflammation, where immune cells like macrophages play a crucial role. Efferocytosis, the process by which apoptotic cells are cleared, is involved in regulating inflammation. However, the role of efferocytosis in AAA pathogenesis remains largely unexplored. A combination of bioinformatic analysis and experimental validation was employed to investigate the role of efferocytosis-related genes (EFRGs) in AAA pathogenesis. Differentially expressed efferocytosis-related genes (EFRDEGs) were identified using datasets such as GSE47472, GSE57691 and GSE7084. Machine learning techniques, including LASSO, Random Forest and XGBoost were used to identify key biomarkers. Single-cell RNA sequencing were used to explore the interactions between EFRGs and immune cells within the AAA microenvironment. Furthermore, the expression of UCP2 was validated in both human and mouse AAA tissues, and pharmacological inhibition of UCP2 was tested in elastase-induced AAA mouse models. The analysis identified 15 EFRDEGs associated with AAA. Machine learning methods identified UCP2, DUSP5, and IL1B as key diagnostic biomarkers, with the highest predictive accuracy (AUC of 1). Single-cell RNA sequencing revealed that UCP2 is highly expressed in macrophages within AAA tissue compared to controls. Moreover, UCP2 was significantly upregulated in both human AAA specimens and elastase-induced mouse AAA models. Immunofluorescence staining confirmed the colocalization of UCP2 with the macrophage marker F4/80 in AAA lesions. Pharmacological inhibition of UCP2 with Genipin significantly attenuated AAA progression in mice, reducing aortic dilation. This study offers a comprehensive exploration of efferocytosis-related genes in AAA and highlights UCP2 as a potential therapeutic target, providing novel strategies for medical intervention.
Insights
This study identifies key efferocytosis-related genes in abdominal aortic aneurysm (AAA) and highlights UCP2 as a promising therapeutic target. Pharmacological inhibition of UCP2 significantly reduced AAA progression in mouse models.
Area of Science:
- Vascular Biology
- Immunology
- Bioinformatics
Background:
- Abdominal aortic aneurysm (AAA) is a life-threatening condition lacking effective pharmacological treatments.
- Chronic inflammation and macrophage activity are central to AAA pathogenesis.
- The role of efferocytosis, or the clearance of apoptotic cells, in AAA remains poorly understood.
Purpose of the Study:
- To investigate the role of efferocytosis-related genes (EFRGs) in AAA pathogenesis.
- To identify key diagnostic biomarkers and potential therapeutic targets for AAA.
- To explore the expression and function of UCP2 in the AAA microenvironment.
Main Methods:
- Bioinformatic analysis of AAA datasets (GSE47472, GSE57691, GSE7084) to identify differentially expressed EFRGs (EFRDEGs).
- Machine learning algorithms (LASSO, Random Forest, XGBoost) for biomarker identification.
- Single-cell RNA sequencing to analyze EFRG interactions with immune cells.
- Experimental validation in human and mouse AAA tissues, including pharmacological inhibition of UCP2 in mouse models.
Main Results:
- Fifteen EFRDEGs were associated with AAA.
- UCP2, DUSP5, and IL1B were identified as key diagnostic biomarkers with high predictive accuracy (AUC=1).
- UCP2 was highly expressed in macrophages within AAA tissue and significantly upregulated in human and mouse AAA specimens.
- Pharmacological inhibition of UCP2 with Genipin attenuated AAA progression and reduced aortic dilation in mice.
Conclusions:
- Efferocytosis-related genes play a significant role in AAA pathogenesis.
- UCP2 is a potential diagnostic biomarker and a promising therapeutic target for AAA.
- Targeting UCP2 offers a novel strategy for medical intervention in AAA treatment.
