Single-cell RNAseq of Angiotensin II-induced abdominal aortic tissue identifies aneurysm-associated cell clusters in C57BL/6J mice.

Abstract

Abdominal aortic aneurysms (AAAs) are life-threatening due to the rupture of aorta. Different vascular cell types are known to be involved in AAA development. However, whether any specific cell cluster plays a critical role during AAA formation is unknown. Angiotensin II (Ang II) infused mouse AAA models are commonly used to study the development and progression of AAA. We here investigate the incidence of AAA at different ages or different doses of Ang II in C57BL/6J mice. There was no AAA formation at a concentration of 1.44 mg/kg/day or 2.16 mg/kg/day at the age of 14 weeks. At the age of 20 weeks and 32 weeks, the incidence of AAA was 18.2% (6/21) and 57.1% (4/7), respectively, with a concentration of 1.44 mg/kg/day. Using single-cell RNA sequencing, we found that increased clusters of monocytes and neutrophils, macrophages, T cells, and B cells were the typical changes in AAA. A special cluster transformed from endothelial cells (malignant ECs) was identified, in which genesinvolved in lipid metabolism, including Cd36, Lpl, Gpihbp1, Fabp4, and Pparg, were highly expressed. Mice receiving Ang II treatment without AAA development showed increased fibroblasts, which may prevent the occurrence of AAA. Through cell-cell interaction analysis, we found that the Cxcl12-Cxcr4/Ackr3 axis, which functions in inflammatory ligand- receptor binding, may play a role in AAA formation. Our results reveal that specific cell clusters may contribute to the progression or prevention of AAA formation. These findings provide new clues for the pathogenesis and intervention of AAA.