The human body is under constant construction. Cells are created to strengthen walls and destroyed to allow for new growth. But new research from OMRF shows that a genetic mishap can cause the process to go awry—and with deadly consequences.
In a paper published this week in the journal PLOS Genetics, senior author and OMRF scientist Courtney Griffin, Ph.D., explains how a protein called CDH4 is integral to maintaining structural integrity around blood vessels. Without the protein, the support structure for blood vessels is weak, and vessels are fragile.
“We tend to think of our bodies as a solid mass, but in between our cells is something called an extracellular matrix,” Griffin said. “It’s kind of like the concrete that holds everything together.”
In order for new blood vessels to grow, that matrix has to be broken down and rebuilt. But too much matrix breakdown can leave vessels susceptible to rupture because they cannot withstand the powerful pressure of blood flowing inside them. The protein CHD4 prevents excessive matrix breakdown.
“Using mouse embryos, we were able to observe what happens when you remove the gene that makes that protein,” she said. “It’s kind of like when you aim for the brakes but hit the gas accidentally. Instead of slowing down matrix degradation, it speeds it up.”
Excessive matrix breakdown is especially dangerous when it occurs around large blood vessels located in the abdomen.
“If a patient experiences an abdominal aortic aneurysm, it can be deadly,” Griffin said. “The vessel balloons and, if it ruptures, it can spill a great deal of blood into the abdominal cavity. It can kill in minutes.”
Griffin said she hopes her work understanding the causes of matrix breakdown in mouse embryos can lead to some therapeutic guideposts to help doctors predict and prevent those aneurysms in adult humans.
OMRF graduate student Kyle Ingram was lead author of the paper. Additional research was done by Florea Lupu, Ph.D., Robert Silasi-Mansat, Ph.D. and Carol Curtis, Ph.D.
Funding for the project was provided by grants No. R00HL087621 from the National Heart, Lung and Blood Institute and No. P20GM10344 from the National Institute of General Medical Sciences, part of the National Institutes of Health. Additional funding came from grant No. HR11-013 from the Oklahoma Center for the Advancement of Science and Technology.