Dr. Nathan D. Airhart, Washington University School of Medicine, St. Louis, was the recipient of this year’s SVS Foundation Resident Research Prize Paper, which was presented at the Vascular Annual Meeting as part of the William J. von Liebig Forum, which features the best in resident research.
Dr. Airhart, his mentor, Dr. John A. Curci, and his colleagues studied the specific contribution of the vascular smooth muscle cells (SMCs) to the destruction of the elastic proteins that are uniquely absent in the walls of abdominal aortic aneurysms (AAAs). “Although the SMC is the dominant cell type in the aortic wall, our understanding of the role of these cells in aneurysms has been very limited,” said Dr. Airhart.
To directly study the function of these cells, Dr. Airhart and his colleagues embarked on an ambitious project to isolate live SMCs from AAAs, normal abdominal aorta (NAA), and plaque from carotid endarterectomy (CEA) procedures. The group profiled the mRNA produced by these cultured cells by microarray and clearly demonstrated a unique pattern of expression of the AAA-SMC.
“The mRNA profiles confirmed that the AAA cells were likely interacting with the matrix differently than the other SMCs, but it did not necessarily tell us how they were influencing aneurysm development,” said Dr. Airhart. To better understand the role of these cells, the investigators evaluated the ability of these cells to break down elastic fibers in culture.
Under standard culture conditions, AAA-SMCs were able to degrade three times more elastin than the NAA-SMCs. “Even more remarkable was the finding that co-culture with activated macrophages – a cell type always found in the wall of aneurysms – resulted in a further doubling of the elastic fiber damage by the AAA-SMCs. Co-culture of macrophages with NAA-SMCs had no effect on the elastin degraded,” said Dr. Airhart.
Further experiments suggested that the enzymes principally responsible for the elastolytic activity of these cells are the matrix metalloproteinases (MMPs). Increases in the production and/or activation of MMP-2 and/or MMP-9 were prominently found in cultures of AAA-SMCs.
“These studies present the strongest evidence that AAA-SMCs exhibit a disease-specific gene expression pattern and can very potently damage the elastic fiber matrix in the aortic wall. The unique and remarkable synergy with activated inflammatory cells might help explain the characteristic elastin loss of aortic aneurysms. Future studies will allow us to understand and alter the cellular mechanisms which lead to increased production and activation of elastolytic MMPs by these cells,” Dr. Curci concluded.
The prestigious Resident Research Prize is intended to motivate new physicians to pursue vascular research. The prize recipient is invited to present his or her research results at the Society for Vascular Surgery’s Vascular Annual Meeting and the prize includes a 1-year subscription to the Journal of Vascular Surgery.