Heart Defects that Lead to Aneurysms Studied by Engineers

Elastin and collagen cross-link throughout the body, as shown here in healthy cardiac tissue. Engineers at Washington University in St. Louis say better understanding of both the mechanical and chemical attributes of a genetic defect that impact those cross-links could lead to a better understanding of how to prevent certain types of aneurysms. (Washington University in St. Louis)

Elastin and collagen are the body’s building blocks. They provide strength and elasticity for many organs, muscles, and tissues. Genetic mutations short circuit their function and can have a devastating and often times lethal, health impact on a person.

New research led by engineers at Washington University in St. Louis is taking a closer look at the genetic and mechanical attributes in order to understand disorders that affect elastin and collagen function.

"Collagen and elastin are everywhere," said Jessica Wagenseil, associate professor of mechanical engineering & materials science at the School of Engineering & Applied Science. "They are in your blood vessels, your skin, your lungs. If they are not working properly, you can have problems in any of these organs."

The study and novel approach focused on the genetic signaling and mechanical effects of mutations on lysyl oxidase or LOX. LOX is made of a copper enzyme, which cross-links collagen and elastin. Lack of this compound has been linked to a higher aortic aneurysm risk in humans.

Wagenseil and her team at Washington University School of Medicine set out to learn more about how LOX deficiency can lead to an aneurysm by examining tissue taken from mice born without LOX and compared it to tissue taken from healthy mice. The LOX-deficient mice showed changes in mechanical behavior and in signaling of groups of genes that were susceptibility differentiators in certain sections of tissue. The way they interacted seemed to provide protection against an aneurysm.

"We're really interested in how the cells respond to major changes in mechanics," Wagenseil said. "So when you take out this enzyme, and you have elastin and collagen that aren't cross-linked, they have totally different mechanical behavior. We expect to see those mechanical differences, but we found that there's this combination of the mechanics and the gene signaling that work together to lead to an aneurysm. We're trying to understand signals that initiate aneurysms. We examined the chemo-mechanical environment, looked at the two factors and how they worked in synch and changed together, which leads to the disease."

The next step for Wagenseil’s research is to determine the role of inflammatory agents in LOX-deficient aneurysms. This study was published in the journal Heart and Circulatory Physiology.