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Possible Link between Diabetes and the Hardening of Heart Valves

High blood glucose levels over a long time might be responsible for aortic valve calcification…

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A correlation between diabetes and calcification of aortic valves was established in 2006. A Rice University lab, in collaboration with the University of Texas Health Science Center at Houston (UTHealth) Medical School, has now discovered that the interstitial cells that turn raw materials into heart valves need just the right amount of nutrients for proper metabolic function. An unexpected discovery was that feeding them too much glucose slowed the cells down.

“The most significant result of the study is that high glucose concentration can actually be detrimental to the aortic-valve cells and their behavior in interacting with the extracellular matrix,” said lead author Peter Kamel, who carried out the experiments as a Rice undergraduate. “We’ve seen in a variety of other cell types, like cells in the kidney, the retina and nerves, that high glucose concentrations can directly damage those cells and their activities. That results in patients with diabetes having problems with vision and with their nerves and kidneys as well.

“The results that high glucose concentration can also cause pathologic remodeling by the aortic-valve cells could suggest that diabetes is also directly a cause of aortic-valve disease.”

Kamel started with solutions of collagen, the most abundant protein in the body, and cells drawn from the aortic heart valves of pigs. Most solutions also included a nutrient — glucose, pyruvate, glutamine or a supplement mixture called F-12 — to stimulate the cells’ metabolism.

When the cells worked at peak, Jane Grande-Allen of Rice’s bioengineering department said, they would contract the liquid into a gel as they absorbed and metabolized nutrients, and then turned raw collagen into connective tissue. “The cells pulled the collagen together and tightened it into packed structures,” she said. “This test is extremely sensitive to how much glucose you give the cells. When we didn’t give them any glucose, nothing happened. If we gave them just a little, we would wait and wait. Sometimes, after about two weeks, the cells would start contracting.

“Glucose helps cells do many things. It provides essential fuel for their function, and it helps them make carbohydrates that are part of glycoproteins and proteoglycans and glycolipids, but the cells have to work really hard to process all that,” Grande-Allen said. “Maybe that’s what’s happening to the collagen gel contraction when we give them more glucose.”

The researchers found solutions with 2 grams of glucose per liter were optimal for contraction. Because off-the-shelf solutions come in standard concentrations of 1 and 4.5 grams per liter, researchers who don’t mix their own solutions could easily miss the connection between glucose level and metabolism, Kamel said.

“It’s interesting that the standard concentrations weren’t the best,” Grande-Allen said.

Practice Pearls:

  • Kamel and colleagues looked at effects of high glucose level on hardening of aortic valves.
  • Results showed that high glucose level could cause remodeling of aortic valves.

Kamel, Peter et al. “Metabolic Regulation of Collagen Gel Contraction by Porcine Aortic Valvular Interstitial Cells.” Journal of the Royal Society Interface, (2014). 10.1098/​rsif.2014.0852