Hardening of the arteries is commonly associated with diseases such as atherosclerosis, where fat deposits and plaques build up in the arterial walls of ailing patients. But arteries can also harden due to abnormal mineralization, a complication often seen in patients with chronic kidney disease or diabetes. This affects the heart, as arteries can no longer pump blood efficiently through the body.
Normal mineralization is a vital and tightly-regulated process that occurs in our bones and teeth. Calcium phosphates are removed from the blood and deposited along collagen fibrils present within the bone. The minerals form crystals that nucleate and grow along the fibrils, eventually interlinking them and giving bones their unique rigidity and tensile strength.
But abnormal mineralization can happen in other parts of the body, such as in the soft tissues of arterial walls, causing them to calcify and harden.
The underlying molecular mechanism that leads to the diseased state of arterial mineralization is poorly understood. In an effort to dissect the process in its early stages, researchers from Canada’s McGill University have examined diseased arteries from genetically modified mice.
Team leader Marta Cerruti hopes that their findings could lead to better early intervention strategies.
“Maybe if we can stop the nucleation, we might be able to stop arterial mineralization,” she said.
“An interdisciplinary approach will be needed to solve this age-old problem.”
Arterial walls owe their elasticity to protein fibres called elastin. They also comprise collagen, which was widely understood to be responsible for abnormal arterial mineralization.
However, in a previous study led by co-author Monzur Murshed, the researchers found that the component of the arteries that initiates calcium phosphate crystallization was elastin. This surprised Cerruti, as the results indicated that a different pathway from bone mineralization causes crystal nucleation in arteries.
“The first part that mineralizes in the arteries of our genetic model is the elastin part and not collagen,” said Cerruti.
“To me that was really surprising. The part that mineralizes in bone and teeth is collagen. Since collagen is also present in the arteries, you would think collagen must have really specific properties that aid that process, so why do the minerals instead get deposited in association with elastin in arteries?”
Cerruti’s team of researchers works to understand surface phenomena at the interface of biological molecules and synthetic surfaces. In the current study, the researchers used the CLS’s SXRMB beamline and found early-stage calcium crystals in the elastin fibres of diseased mice.
The results were published in the February 2018 edition of Arteriosclerosis, Thrombosis, and Vascular Biology. The study concludes that a possible strategy to prevent vascular calcification may involve therapeutics which block mineral accumulation.
An effective way to do so would be to intervene in the early stages of calcium phosphate crystallization. Cerruti and Murshed are currently working on developing this intervention strategy for possible therapeutic applications.
Source: Press Release, McGill University