TO TEASE OUT THE COMPLEX INTERPLAY of immunity and atherosclerosis (hardening of the arteries), biomedical researcher Stephen Ramsey has designed software that can analyze both gene expression measurements and genetic information. With this new tool, he and his interdisciplinary team have found a significant increase in heart disease among animals deficient in a particular protein that regulates the immune system.
“Cardiovascular disease is just the tip of the research iceberg,” says Ramsey, an assistant professor of systems biology and bioinformatics at Oregon State University. “Tuberculosis, vaccination response and many other pressing health issues are ripe for this technology.”
His basic research question is, How does the human immune system affect the development of atherosclerosis? In particular, he wants to learn the role of “macrophage cells” — cells that attack foreign substances in the body. When stimulated by oxidized LDL cholesterol (the “bad” cholesterol), these cells contribute to the development of plaque on artery walls.
“Certain proteins – called transcription factors – control the on and off switch of genes,” says Ramsey, who holds dual appointments in the colleges of Veterinary Medicine and Engineering. “When macrophages are stimulated by oxidized LDL, different sets of genes are activated or deactivated.”
The new software gives researchers much more capacity to handle the massive amounts of data generated by high-speed robotic DNA sequencing. For their study, Ramsey and his collaborators used a mouse strain that is genetically deficient in the “ATF3” protein, which regulates the immune system. This deficiency makes the animals more susceptible to atherosclerosis.
So far, the Ramsey Lab and collaborators have identified eight transcription factors that are linked to lowering LDL in the blood. His team’s findings suggest that one of these transcription factors (called TCF/LEF) is involved in directing plaque-causing macrophages to leave the artery wall, a required step in the process of reversing atherosclerosis. Long-term, he hopes to use his discoveries to develop new therapies for the prevention and treatment of atherosclerosis.
–Story by Lyn Smith-Gloria, OSU College of Veterinary Medicine