The interesting research noted here implicates pressure-based changes in the structure of vitronectin as a mediating mechanism linking raised blood pressure and ocular pressure and calcification in tissues. Calcification results from changes in cell behavior that lead to calcium deposition akin to that occurring in bone tissue, but in inappropriate locations such as blood vessel walls. This is disruptive of structure and function, a facet of aging that should be addressed as a part of any comprehensive package of rejuvenation therapies.
"Proteins in the blood are under constant and changing pressure because of the different ways blood flows throughout the body. For example, blood flows more slowly through small blood vessels in the eyes compared to larger arteries around the heart. Blood proteins need to be able to respond to these changes, and this study gives us fundamental truths about how they adapt to their environment, which is critical to targeting those proteins for future treatments."
There are hundreds of proteins in our blood, but the researchers focused on vitronectin, one of the most abundant. In addition to circulating in high concentrations in the blood, vitronectin is found in the scaffolding between cells and is also an important component of cholesterol. "This protein is an important target for macular degeneration because it accumulates in the back of the eye, causing vision loss. Similar deposits appear in the brain in Alzheimer's disease and in the arteries in atherosclerosis. We want to understand why this happens and leverage this knowledge to develop new treatments."
To approach this question, the researchers were interested in learning how the protein changes its structure at different temperatures and under different levels of pressure, approximating what happens in the human body. Through detailed biochemical analysis, the researchers found that the protein can subtly change its shape under pressure. These changes cause it to bond more easily to calcium ions in the blood, which the researchers suggest leads to the buildup of calcified plaque deposits characteristic of macular degeneration and other age-related diseases. "It's a very subtle rearrangement of the molecular structure, but it has a big impact on how the protein functions. The more we learn about the protein on a structural and mechanistic level, the better chance we have of successfully targeting it with treatments."