A study published in Translational Research reveals that the nuclear receptor NOR-1 plays a key role in regulating the calcification of aortic valves and calcification associated with atherosclerosis. The work was led by José Martínez-González, a researcher at the Institute of Biomedical Research of Barcelona (IIBB-CSIC) and the Sant Pau Research Institute, and Cristina Rodríguez Sinovas, a researcher at the Sant Pau Research Institute, both affiliated with the cardiovascular diseases area of CIBER (CIBERCV). The CIBERCV team led by Francisco Marín from the Virgen de la Arrixaca University Clinical Hospital also collaborated.
“So far, we knew about NOR-1’s role in cardiac and blood vessel remodeling, but its connection to calcification in these tissues had not been established,” explains Dr. Martínez-González.
The study conducted analyses on human aortic valves and vascular cells, as well as on a genetically modified mouse model with elevated NOR-1 levels in the vascular wall. These mice showed a reduction in atherosclerosis development, lower vascular expression of osteogenic markers, and specifically, reduced vascular calcification.
“NOR-1 limits cardiovascular calcification, a complex, partially characterized process that poses a significant public health problem. Our analyses of human samples from aortic valves and calcified atherosclerotic lesions, studies on valve and vascular cells, and in vivo strategies demonstrate NOR-1’s involvement in regulating the complex network of genes contributing to cardiovascular calcification,” notes Dr. Rodríguez Sinovas.
The research team observed that cells responsible for calcium deposition in aortic valves and smooth muscle cells in arteries increase NOR-1 levels when calcification is induced. “When we increased or decreased NOR-1 levels in these cells, we saw significant changes in genes related to calcification.”
Until recently, vascular calcification was considered a passive and degenerative process associated with advanced age, atherosclerosis, various metabolic disorders like diabetes mellitus, or rare genetic diseases. However, in recent years, vascular calcification is viewed as an active and regulated process similar to bone mineralization and metabolism.
“Our data indicate that NOR-1 has a negative effect on the expression of genes related to calcification in both heart valve cells and arterial cells, and it prevents calcification in the cardiovascular system. This could have significant implications for the treatment of cardiovascular diseases,” adds Carme Ballester, the study’s lead author.
“The results enhance our understanding of the processes leading to ectopic mineralization and pave the way for future studies that will create new therapeutic opportunities in the fight against cardiovascular calcification,” concludes the team.
Carme Ballester-Servera, Laia Cañes, Judith Alonso, Lidia Puertas-Umbert, Paula Vázquez-Sufuentes, Manel Taurón, Elena Roselló-Díez, Francisco Marín, Cristina Rodríguez, José Martínez-González. Upregulation of NOR-1 in calcified human vascular tissues: impact on osteogenic differentiation and calcification. Translational Research (2023) – https://www.sciencedirect.com/science/article/pii/S1931524423001445?via%3Dihub
