The disease process usually begins with an immune system response to an insult or injury to the arterial lining, said Goldschmidt. Once there, these cells recruit lipids and other fatty materials to the damage site, essentially creating a scar. Over time, the affected arterial cells themselves change, creating a narrower and less elastic artery.
The Duke team focused on the role of a specialized bone marrow cells known as vascular progenitor cells (VPC). These cells circulate throughout the blood stream, respond to the initial damage to the arterial lining and initiate the repair process.
"In our latest experiments, we have demonstrated the natural molecular history of atherosclerosis based on the expression of distinct gene clusters and how changes in VPCs are associated with the progression of disease," said Duke cardiologist David Seo, M.D., senior author of the paper. "This is the first time the progression of a chronic disease has been linked to changes in the body's ability to repair itself."
For their experiments, the researchers used a well-studied strain of mice whose responses to arterial damage closely parallel that of humans. They fed the mice high-fat diets at different ages. Based on the level of disease found in the aortas of mice, they classified the mice as having no disease, early disease, intermediate disease and moderate disease.
The researchers then performed a DNA microarray, or gene chip, analysis of the activity of genes in aorta samples from each of the four groups. Using this novel technique, researchers can quickly screen more than 12,500 known genes, searching for those that are "turned on," or expressing themselves.
"We found distinct gene clusters, or what we call metagenes, that were activated in each group," said Ravi Karra, M.D., first author of paper and member of the Duke team as a medical student. He is now conducting residenc
Contact: Richard Merritt
Duke University Medical Center