Cross-sectional images of the aorta showing fragmented elastin in Fbln4E57K/E57K mice compared to littermate controls (Fbln4+/+ and Fbln4+/E57K).
Genetics and other causes may cause the body's largest artery, the aorta, to widen or expand, leading to weakness in its walls. This weakness may lead to a thoracic aortic aneurysm, or a rupture causing extensive damage and bleeding.
With a three-year, $300,000 Transformational Project Award from the American Heart Association, Jessica Wagenseil, associate professor of mechanical engineering & materials science in the McKelvey School of Engineering at Washington University in St. Louis, will study how change in the structure of the artery's wall may contribute to the progression of an aneurysm.
Wagenseil studies the function of the protein elastin, which gives arteries their elastic properties. With the new funding, she will assess whether the loss of physical integrity of the elastic layers in the artery wall alters its function and allows proteins and inflammatory cells in the blood to filter through, eventually leading to development of the aneurysm and eventual failure. These aneurysms can be treated with medications or drug-coated stents, Wagenseil said.
To study this process, she and her team, including Austin Cocciolone, a postdoctoral research associate in her lab, will look at novel mouse models that have mutations in the elastic fiber genes fibulin-4 and lysyl oxidase, both known factors underlying thoracic aortic aneurysms in humans. Another factor is dysfunction in endothelial cells, which reduces the integrity of the artery wall.
Cocciolone, who earned a doctorate in biomedical engineering from the McKelvey School of Engineering in May 2019, showed in his doctoral dissertation that molecules move across the artery wall differently in a disease model than a normal model.
"We will measure how things move across the artery wall, and we think that in these disease models, both cytokines and cells will move across easier," Wagenseil said. "That could have a lot of effect on how fast a drug moves across the wall, how long it stays, or how much should be put in the stent."
The Transformational Project Awards support highly innovative, high-impact projects that build on work in progress that could ultimately lead to critical discoveries or major advancements that will accelerate the field of cardiovascular and stroke research.
The McKelvey School of Engineering at Washington University in St. Louis focuses intellectual efforts through a new convergence paradigm and builds on strengths, particularly as applied to medicine and health, energy and environment, entrepreneurship and security. With 96.5 tenured/tenure-track and 33 additional full-time faculty, 1,300 undergraduate students, 1,200 graduate students and 20,000 alumni, we are working to leverage our partnerships with academic and industry partners — across disciplines and across the world — to contribute to solving the greatest global challenges of the 21st century.