期刊
FRONTIERS IN CARDIOVASCULAR MEDICINE
卷 8, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fcvm.2021.751525
关键词
in-stent restenosis; single-cell sequencing; vascular smooth muscle cell; transitional-cell; neointimal hyperplasia
资金
- National Natural Science Foundation of China (NSFC) [81970307, 81801147]
- Six Talent Peaks Project of Jiangsu Province [2019-WSN-156]
- Social Development Project of Jiangsu Province [BE2019616]
- Jiangsu Commission of Health [H2019077]
- Nanjing Commission of Health [ZKX19027]
- Nanjing Health Youth Talent Training project [QRX17017]
This study mapped potential cellular targets of neointimal hyperplasia by comparing normal and stenotic arteries, and highlighted the crucial role of VSMC phenotype switching in the progression of neointimal hyperplasia. Additionally, several novel target genes were proposed through disease susceptibility gene analysis, such as Cyp7a1 and Cdk4.
Aims: In-stent restenosis (ISR) remains an Achilles heel of drug-eluting stents despite technical advances in devices and procedural techniques. Neointimal hyperplasia (NIH) is the most important pathophysiological process of ISR. The present study mapped normal arteries and stenotic arteries to uncover potential cellular targets of neointimal hyperplasia.Methods and Results: By comparing the left (control) and right (balloon injury) carotid arteries of rats, we mapped 11 clusters in normal arteries and 11 mutual clusters in both the control and experimental groups. Different clusters were categorized into 6 cell types, including vascular smooth muscle cells (VSMCs), fibroblasts, endothelial cells (ECs), macrophages, unknown cells and others. An abnormal cell type expressing both VSMC and fibroblast markers at the same time was termed a transitional cell via pseudotime analysis. Due to the high proportion of VSMCs, we divided them into 6 clusters and analyzed their relationship with VSMC phenotype switching. Moreover, N-myristoyltransferase 1 (NMT1) was verified as a credible VSMC synthetic phenotype marker. Finally, we proposed several novel target genes by disease susceptibility gene analysis, such as Cyp7a1 and Cdk4, which should be validated in future studies.Conclusion: Maps of the heterogeneous cellular landscape in the carotid artery were defined by single-cell RNA sequencing and revealed several cell types with their internal relations in the ISR model. This study highlights the crucial role of VSMC phenotype switching in the progression of neointimal hyperplasia and provides clues regarding the underlying mechanism of NIH.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据