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University of Virginia Researchers Uncover Mechanism Behind Renin Production
Charlottesville, VA – In a groundbreaking study, researchers at the University of Virginia (UVA) School of Medicine have unveiled a critical mechanism by which certain cells transform their function to help regulate blood pressure through the production of renin, a vital hormone typically produced by specialized kidney cells. This discovery, published in the journal Hypertension, could pave the way for innovative treatments for hypertension and related vascular diseases by targeting the genomic “switch” that governs renin production.
Smooth muscle cells, which line blood vessels and help control blood pressure by contracting and relaxing, exhibit a remarkable adaptability. When blood pressure falls significantly over extended periods, these cells in the kidneys—and other kidney cell types—can switch roles, beginning to produce renin. This transformation has puzzled scientists for years, but the UVA team has pinpointed the genomic triggers behind this crucial shift.
“Discovering how the switch works will help us understand how our bodies control blood pressure,” stated Dr. R. Ariel Gomez, a leading researcher from UVA’s Child Health Research Center. “Understanding how vascular cells change their identity could lead to the development of new medications for high blood pressure and vascular diseases.”
Dr. Gomez and his collaborator, Dr. Maria Luisa S. Sequeira-Lopez, along with UVA senior scientist Dr. Jason P. Smith, delved into the role of renin in blood pressure regulation. Their research focused on how specific cells can “remember” to produce renin long after they have ceased to do so. Through their investigations, the team identified nine key genes that are crucial to three biological pathways regulating renin production.
These genes dictate when smooth muscle cells stop and resume renin production, with researchers noting that while these cells may naturally cease renin production, they remain “poised” to reactivate when needed.
The study also highlighted the discovery of an epigenetic switch that controls this process. Contrary to expectations that the gene’s regulatory region would be inaccessible when renin production is off, researchers found it remains accessible in cells that can quickly respond to demands for renin.
Dr. Smith remarked, “Ultimately, since renin is so critical for our health, a better understanding of how our bodies control its production may prove foundational in treating hypertension and understanding the long-term effects of common blood pressure medications on kidney function and disease.”
This comprehensive mapping of renin regulation provides a valuable framework for future research, with potential implications for preventing dangerous kidney damage known as fibrosis. The researchers believe that targeting the mechanisms controlling renin production could lead to new therapies for high blood pressure and cardiovascular diseases.
“Now we want to identify markers and potential targets to mitigate and hopefully control unwanted effects of chronic stimulation of the renin cells,” Dr. Sequeira-Lopez emphasized. “Understanding the basic secrets of our cells is crucial for designing more effective therapies with fewer or no adverse effects.”
The research was supported by the National Institutes of Health under grants P50DK096373, R01DK116718, and R01HL148044.
For more details, refer to the study titled “Inhibition of Renin Expression Is Regulated by an Epigenetic Switch From an Active to a Poised State” by Jason P. Smith et al. (July 11, 2024). DOI: 10.1161/HYPERTENSIONAHA.124.22886.
