Single‐Cell RNA‐Seq Reveals Injuries in Aortic Dissection and Identifies PDGF Signalling Pathway as a Potential Therapeutic Target

• Published in: Journal of cellular and molecular medicine 2024-12, Vol.28 (24), p.e70293-n/a
• Main Authors: Han, Yichi, Cui, Yongji, Liu, Juli, Wang, Dingchen, Zou, Guoxiang, Qi, Xin, Meng, Jinxiu, Huang, Xiaoran, He, Haiwei, Li, Xin
• Format: Article
• Language: English
• Subjects: Antibodies; Aorta; Aorta - metabolism; Aorta - pathology; Aortic dissection; Aortic Dissection - genetics; Aortic Dissection - metabolism; Aortic Dissection - pathology; CD4 antigen; Cell cycle; Cell death; Cell differentiation; Cell Differentiation - genetics; cellular heterogeneity; Connective tissue; Coronary vessels; Disease; Dissection; Extracellular matrix; Females; Genotype & phenotype; Growth factors; Hospitals; Humans; Lymphocytes T; Male; Marfan syndrome; Molecular modelling; Muscle contraction; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - pathology; Myocytes, Smooth Muscle - metabolism; Original; Oxidative Stress; Pathogenesis; Patients; Phenotypes; Platelet-Derived Growth Factor - genetics; Platelet-Derived Growth Factor - metabolism; RNA-Seq - methods; Senescence; Signal Transduction; Single-Cell Analysis - methods; Single-Cell Gene Expression Analysis; single‐cell RNA sequencing; Smooth muscle; Stem cells; Therapeutic targets
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/jcmm.70293

ABSTRACT Aortic dissection (AD) represents a critical condition characterised by a tear in the inner lining of the aorta, leading to the leakage of blood into the layers of the aortic wall, posing a significant risk to life. However, the pathogenesis is unclear. In this study, scRNA‐seq was applied to cells derived from aortas of both AD and non‐AD donors (control) to unveil the cellular landscape. ScRNA‐seq data uncover significant cellular heterogeneity in AD aortas. Specifically, we observed an accumulation of CD4+ T cells, which contributed to inflammation and cell death, and abnormal collagen formation mediated by fibroblast cells in AD. Moreover, we revealed a greater prevalence of cell death, oxidative stress and senescence in AD aorta cells. Furthermore, we found a decrease in the percentage of vascular stem cells (VSCs), along with a repression in their ability to differentiate into contractile vascular smooth muscle cells (VSMCs). Finally, our data demonstrated that the PDGF signalling pathway was activated in AD. We found that PDGF activation could lead to VSMCs aberrant switch from contractile to synthetic phenotype, which could be ameliorated by PDGF inhibitor. This underscores the potential of the PDGF as a therapeutic target for AD. In summary, our study highlights the cellular heterogeneity and associated injuries within aortas affected by AD, including cell death, oxidative stress, senescence and dysregulation of signalling pathways influencing the aberrant phenotypic switch of VSMCs. These insights offer valuable contributions to understanding the molecular mechanisms underlying AD and present new avenues for therapeutic intervention in this condition.