image: A. Diagram of Workflow Design; B. Single-cell Atlas of Cardiac Cells; C. Single-cell Atlas of Non-immune Cell Subpopulations; D. Single-cell Atlas of Immune Cell Subpopulations; E. Expression of Iron and Oxidative Stress in CAC and Normal Samples; F. Expression of Damage Marker Genes in Endothelial Cell Subpopulations; G. Scores of Immune Activation and Pro-inflammatory Modules in Immune Cell Subpopulations; H. Scores of Cellular Metabolic Pathways in the Hypercoagulable Phase, Fibrinolysis Phase, and Normal Group of CAC
Credit: ©Science China Press
The project is led by Professor Wang Guoqing of the School of Basic Medicine and Professor Qiu Jiazhang of the School of Veterinary Medicine of Jilin University. In this study, they performed single-cell sequencing analysis of the right ventricular free wall tissue from healthy donors, patients who died during the hypercoagulable period of characteristic coagulation abnormality (CAC), and patients who died during the fibrinolytic period of CAC. They collected 61,187 cells enriched in 24 immune cell subsets and 13 cardiac-resident cell subsets. They found that in the course of SARS-CoV-2 infected heart microthrombus, MYO1EhighRASGEF1Bhighmonocyte-derived macrophages promoted hyperactivation of the immune system and initiated the extrinsic coagulation pathway by activating chemokines CCL3, CCL5. This series of events is the main cause of cardiac microthrombi following SARS-CoV-2 infection. In a SARS-CoV-2 infected heart microthrombus, excessive immune activation is accompanied by an increase in cellular iron content, which in turn promotes oxidative stress and intensifies intercellular competition. This induces cells to alter their metabolic environment, resulting in increased sugar uptake via the glycosaminoglycan synthesis pathway. In addition, high levels of reactive oxygen species generated by elevated iron levels promote increased endogenous malondialdehyde synthesis in a subpopulation of cardiac endothelial cells. This exacerbates endothelial cell dysfunction and exacerbates the coagulopathy process.
See the article:
Resolving the developmental mechanisms of cardiac microthrombosis of SARS-CoV-2 based on single-cell transcriptome analysis
https://doi.org/10.1007/s11427-023-2624-9
Journal
Science China Life Sciences