Integrative analysis of single-Cell RNA sequencing and experimental validation in the study of abdominal aortic aneurysm progression

被引：3

作者：

Xiong, Jie ^{[1
]}

Chen, Guojun ^{[2
]}

Lin, Beiyou ^{[1
]}

Zhong, Lintao ^{[1
]}

Jiang, Xiaofei ^{[1
]}

Lu, Hongyun ^{[1
]}

机构：

[1] Jinan Univ, Zhuhai Hosp, Zhuhai Peoples Hosp, Dept Cardiol, Zhuhai 519000, Peoples R China

[2] Southern Med Univ, Nanfang Hosp, Dept Cardiol, 1838 North Guangzhou Ave, Guangzhou 510515, Peoples R China

来源：

GENE | 2024年 / 929卷

关键词：

Single-cell RNA sequencing; Abdominal aortic aneurysm; Vascular smooth muscle cells; Macrophages; Cell-cell interactions; GENE-EXPRESSION; R-PACKAGE; REVEALS; ATHEROSCLEROSIS; VISUALIZATION; INFLAMMATION; MECHANISMS;

D O I：

10.1016/j.gene.2024.148820

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Background: Abdominal aortic aneurysm (AAA) is a complex vascular disorder characterized by the progressive dilation of the abdominal aorta, with a high risk of rupture and mortality. Understanding the cellular interactions and molecular mechanisms underlying AAA development is critical for identifying potential therapeutic targets. Methods: This study utilized datasets GSE197748, GSE164678 and GSE183464 from the GEO database, encompassing bulk and single-cell RNA sequencing data from AAA and control samples. We performed principal component analysis, differential expression analysis, and functional enrichment analysis to identify key pathways involved in AAA. Cell-cell interactions were investigated using CellPhoneDB, focusing on fibroblasts, vascular smooth muscle cells (VSMCs), and macrophages. We further validated our findings using a mouse model of AAA induced by porcine pancreatic enzyme infusion, followed by gene expression analysis and coimmunoprecipitation experiments. Results: Our analysis revealed significant alterations in gene expression profiles between AAA and control samples, with a pronounced immune response and cell adhesion pathways being implicated. Single-cell RNA sequencing data highlighted an increased proportion of pro-inflammatory macrophages, along with changes in the composition of fibroblasts and VSMCs in AAA. CellPhoneDB analysis identified critical ligand-receptor interactions, notably collagen type I alpha 1 chain (COL1A1)/COL1A2-CD18 and thrombospondin 1 (THBS1)-CD3, suggesting complex communication networks between fibroblasts and VSMCs. In vivo experiments confirmed the upregulation of these genes in AAA mice and demonstrated the functional interaction between COL1A1/COL1A2 and CD18. Conclusion: The interaction between fibroblasts and VSMCs, mediated by specific ligand-receptor pairs such as COL1A1/COL1A2-CD18 and THBS1-CD3, plays a pivotal role in AAA pathogenesis.

引用

页数：15