Article Impact Level: HIGH Data Quality: STRONG Summary of Nature Communications, 15(1), 10754. https://doi.org/10.1038/s41467-024-54917-4 Dr. Alexsia Richards et al.
Points
- Smooth muscle cells (SMCs) were identified as the primary targets of infection, triggering pro-inflammatory responses and gene expressions linked to coagulation and vascular complications.
- While endothelial cells were not directly infected, they exhibited significant dysfunction due to signals from infected SMCs, weakening blood vessel integrity and increasing viral susceptibility.
- The drug N, N-Dimethyl-D-erythro-sphingosine successfully reduced infection in SMCs without damaging endothelial cells, suggesting potential therapeutic applications for mitigating vascular damage.
- The vascular effects observed in the stem cell model aligned with clinical data from COVID-19 patients, reinforcing the model’s relevance and accuracy.
- The innovative stem cell model is a valuable resource for studying the vascular impacts of viral infections and testing drug interventions, aiding in the development of treatments for emerging pathogens.
Summary
In this study, researchers examined the vascular effects of SARS-CoV-2 infection using an innovative stem cell model to replicate the virus’s impact on endothelial cells, smooth muscle cells (SMCs), and pericytes, which form the vascular structure. The model revealed that SMCs, rather than endothelial cells, were primarily infected by the virus. This infection triggered a pro-inflammatory response and increased the expression of genes involved in coagulation, which are critical in promoting vascular events like blood clots and stroke. Importantly, endothelial cells did not directly succumb to infection but experienced significant dysfunction through signaling from the infected SMCs, which weakened their intercellular junctions and led to blood leakage and increased susceptibility to viral spread.
The study found that the effects observed in the cell model were consistent with clinical data from patients. Specifically, genes linked to increased vascular complications in severe COVID-19 infections were similarly expressed in the stem cell model. Additionally, the researchers tested a drug, N, N-Dimethyl-D-erythro-sphingosine, which successfully reduced infection in SMCs without harming the surrounding endothelial cells. This finding suggests potential therapeutic avenues for future viral strains that may pose vascular risks, even though the recent omicron strain demonstrated milder vascular effects in both the model and patients.
The researchers’ model provides an invaluable tool for understanding the vascular impact of viral infections and testing potential drugs. It opens the door to future studies on drug interventions to mitigate vascular damage caused by viruses. By focusing on the interaction between SMCs and endothelial cells, this model not only enhances our understanding of SARS-CoV-2’s vascular pathology but could also facilitate the rapid development of treatments for emerging pathogens.
Link to the article: https://www.nature.com/articles/s41467-024-54917-4
References Richards, A., Khalil, A. S., Friesen, M., Whitfield, T. W., Gao, X., Lungjangwa, T., Kamm, R. D., Wan, Z., Gehrke, L., Mooney, D., & Jaenisch, R. (2024). SARS-CoV-2 infection of human pluripotent stem cell-derived vascular cells reveals smooth muscle cells as key mediators of vascular pathology during infection. Nature Communications, 15(1), 10754. https://doi.org/10.1038/s41467-024-54917-4
