Article Impact Level: HIGH Data Quality: STRONG Summary of Nature Communications, 16(1), 429. https://doi.org/10.1038/s41467-024-55687-9 Dr. Moritz Lehners et al.
Points
- The study explores the role of natriuretic peptide signaling in vascular smooth muscle cells (VSMCs) and its influence on atherosclerosis progression, emphasizing the protective effects of the CNP/GC-B signaling pathway.
- A shift from ANP/GC‑A to CNP/GC‑B signaling in VSMCs was linked to the transition of contractile VSMCs into chondrocyte-like plaque cells. Blocking the CNP/GC-B pathway led to increased vascular calcification, highlighting its atheroprotective role.
- Fluorescent biosensors enabled real-time tracking of cGMP production, providing insights into its function and ability to counteract calcification in atherosclerotic plaques.
- Vosoritide, a drug targeting cGMP signaling for dwarfism treatment, may hold promise as a novel therapeutic approach for atherosclerosis and improving vascular health.
- Findings underscore the potential of targeting cGMP pathways to prevent vascular calcification and stiffness, paving the way for innovative treatments for cardiovascular diseases.
Summary
This study investigates the role of natriuretic peptide signaling in vascular smooth muscle cells (VSMCs) and its impact on atherosclerosis progression. Using murine models, the research team focused on the molecular signaling pathways of cGMP, a key regulator of vascular function produced through various pathways in VSMCs. They observed that the shift from ANP/GC‑A to CNP/GC‑B signaling in VSMCs during atherogenesis was associated with a phenotypic change of contractile VSMCs to chondrocyte-like plaque cells. Notably, silencing the CNP/GC-B axis increased the presence of chondrocyte-like plaque cells, suggesting that the CNP/GC-B pathway acts as an atheroprotective regulator. This finding highlights the potential for targeting cGMP pathways to modulate VSMC phenotype and slow atherosclerosis progression.
The study’s use of fluorescent biosensors to track cGMP in real time allowed detailed visualization of its production and role within vascular cells during atherosclerosis. Single-cell analysis demonstrated that the CNP/GC-B pathway activation counteracts the calcification typically seen in atherosclerotic plaques. Blocking this pathway in murine models resulted in more severe vascular calcification, reinforcing the protective role of this signaling axis. These findings suggest that maintaining proper cGMP signaling in VSMCs may prevent or reduce the stiffness and calcification of blood vessels that characterize advanced atherosclerosis.
The research also draws an intriguing parallel between vascular cGMP signaling and bone growth, as the same pathways that promote bone development are involved in regulating vascular health. Vosoritide, a drug that modulates cGMP signaling and treats dwarfism, may have potential applications in atherosclerosis treatment. These insights could pave the way for new therapeutic strategies targeting the cGMP pathway to treat cardiovascular diseases, particularly atherosclerosis, and improve vascular health.
Link to the article: https://www.nature.com/articles/s41467-024-55687-9
References Lehners, M., Schmidt, H., Zaldivia, M. T. K., Stehle, D., Krämer, M., Peter, A., Adler, J., Lukowski, R., Feil, S., & Feil, R. (2025). Single-cell analysis identifies the CNP/GC-B/cGMP axis as marker and regulator of modulated VSMCs in atherosclerosis. Nature Communications, 16(1), 429. https://doi.org/10.1038/s41467-024-55687-9
