A recent study by researchers at the University of Illinois Urbana-Champaign, along with collaborators at UCLA Health and the University of Texas at Austin, has uncovered the body’s advanced defenses against the hardening of heart tissues due to the accumulation of calcium minerals. This study is the first to provide a detailed, step-by-step documentation of how calcification progresses in the body.We conducted a study that provides the first comprehensive, step-by-step documentation of the progression of calcification.
“Heart disease is the leading cause of death each year, with about 18 million deaths annually, and that number is increasing. A large portion of these deaths is due to calcification,” said Bruce Fouke, the leader of the study and a professor at the University of Illinois. “When the aortic valve becomes calcified, the only available option is an extremely invasive surgery to replace the valve. This emphasizes the importance of understanding this process in order to find more effective ways to manage it.”Moving forward with the development and testing of drugs is crucial in the medical field. The aortic valve plays a vital role in pumping oxygenated blood from the heart to the body, and it opens and closes more than 3 billion times in an average lifespan. However, calcium deposits can build up within the valve’s leaflets, causing stiffness and preventing them from opening fully.
Mayandi Sivaguru mentioned that while a stent can help with calcification in blood vessels, it is not an option for the aortic valve. If the aortic valve stops functioning, it can be life-threatening, regardless of the condition of other organs in the body.The lead author of the article and the head of the Cytometry and Microscopy to Omics Facility in the Carver Biotechnology Center. Despite being widely present and biologically important, there is limited understanding of how calcium deposits form and develop. Fouke’s team is at the forefront of the “GeoBioMed” field, which combines geology, biology, and medicine, and has previously used this approach to study kidney stones. In a new research paper published in Scientific Reports, Fouke’s team at Illinois collaborated with colleagues at the UCLA School of Medicine and the Jackson School of Geoscience at Texas to investigate and document the stages of calcium deposition.The researchers examined the formation of calcium phosphate in aortic valves taken from human cadaver hearts using a variety of different methods, such as optical microscopy, electron microscopy, and spectroscopy. This comprehensive approach allowed them to gain new insights into the mineralization and protein distribution in the valves, providing valuable information about cardiovascular calcification. The process begins with healthy leaflet tissue, and then small calcium phosphate spherules develop in the smooth muscle layer of the leaflets. This discovery is crucial in advancing our understanding of cardiovascular health.different from the traditional understanding of mineral formation in bone,” said the lead researcher. “The calcium phosphate in these deposits is not the same as the apatite found in bone. Instead, it is mainly amorphous calcium phosphate, which has unique properties that allow it to change shape and rearrange its atomic structure.” This discovery challenges the widely-held belief about the composition of mineral deposits in the body.
As the spherules continue to develop, they come together to form layers that coat and strengthen the collagen and smooth muscle fibers in the leaflets, enhancing their flexibility. These processes culminate in the formation of large nodules that rotate, come into contact with each other, and further stiffen the tissues.
The lead researcher stated, “Upon further investigation, we observed that the chemical reactions occurring within the valve tissues were significantly different from what has been traditionally understood about mineral formation in bone.” This indicates that the composition of calcium phosphate in the deposits does not align with previous assumptions.Fouke, a professor at the University of Illinois, explained that the mineral-water interactions in our bodies are similar to those seen in coral reefs and hot springs. He pointed out that our blood contains calcium and phosphate, which inevitably leads to the calcification of collagen and the formation of nodules.
However, Fouke also mentioned that our bodies have evolved complex processes to combat this mineralization. While it can’t completely prevent it, the body is able to significantly slow down the process. The researchers discovered two defensive mechanisms that our bodies use to fight against mineralization.The process of ACP spherules forming and coming together causes the heart tissues to produce a lot of osteopontin protein. This protein is known for promoting apatite growth and calcification in bones and kidney stones, which initially confused the researchers. However, it was discovered that osteopontin actually has an inhibitory effect on ACP, slowing down collagen calcification and nodule aggregation.
Understanding that it’s ACP instead of apatite is crucial. It could be important to increase the release of osteopontin as a new target to slow down calcification to a level where it won’t be a threat or require surgical intervention, according to Fouke.The body’s second line of defense against nodules forming is the collagen, which stretches around and contains them, creating a barrier to slow their growth. Researchers are looking at how osteopontin could be used to slow down calcification, and they hope their work will lead to new ways to prevent the growth of mineral deposits in the human body. They are working with the Mayo Clinic to further develop their research.The GeoBioMed approach is used to study calcification in human breast tumors, which is a key characteristic of the disease. This work was supported by The Barbara and Ed Weil Foundation, the National Institutes of Health (grant OT2OD023848), and the UCLA Amara-Yad project.
