The cardiovascular system loses its flexibility with age, a process thought to be related to a build up of cross-links, calcium deposits, and other unwanted compounds in the extracellular matrix. Reversing this portion of age-related degeneration should be a comparatively straightforward matter of building drugs to break down or remove these metabolic byproducts. Researchers here investigate another possible culprit in the process:
Heart valves calcify over time, and [scientists] are beginning to understand why. [They] found through studies of pigs' heart valves that age plays a critical role in the valves' progressive hardening, and the problem may be due to the infiltration of a protein known as von Willebrand factor (VWF). VWF helps regulate blood clotting in both pigs and humans but [it] finds its way over time into the collagen-rich interior of the valve tissues. Because clotting is not an issue in collagen, there is no apparent need for VWF to be present. The researchers went looking for a connection to the calcium nodules that form in the tissues and make the valves' leaflets less flexible, which decreases blood flow to the heart.
[Researchers] tested how valve interstitial cells that produce calcium nodules in diseased valves respond to VWF. When interstitial cells were intentionally exposed to VWF, "there was a dramatic increase in the size of the nodules at every age. Endothelial cells on the outside of the valve are making most of these (clotting-related) proteins. We found they don't just float away into the blood or stay on the valve surface. Some of them penetrate down into the tissue."
What remains to be seen is why. Heart valves are in motion from birth to death and are perhaps the most active connective tissue in the body. The researchers suspect the breakdown of collagen over time, as well as the constant stretching of the valve, opens gaps through which the proteins can travel. "As you get older, collagen becomes less organized. Because the distinct arrangement of extracellular matrix disappears, I think proteins like VWF permeate inside the valve more than what you would see in young, healthy adults."