For the past seven years, Thompson's group has explored the relationship between enzymes called matrix metalloproteinases (MMPs) and abdominal aortic aneurysms. These protein-destroying enzymes are secreted by white cells called macrophages, which fight infection but also can harm host tissues. Two MMPs -- MMP-2 and MMP-9 -- are under suspicion because they are much more abundant in aneurysm tissue than in healthy artery wall. They also attack elastin, a protein that helps strengthen the wall, enabling it to withstand the force of the heart's pumping. "It is believed that the breakdown of elastin and another key protein, collagen, allows an abdominal aortic aneurysm to form and then to grow," Thompson says.
He thought doxycycline might be a useful drug because this chemical cousin of tetracycline was known to inhibit MMPs -- it now is being tested in clinical trials for patients with gingivitis, osteoarthritis and rheumatoid arthritis, three connective tissue diseases. "We were interested because our group operates on 150 to 200 patients with abdominal aortic aneurysms each year, and the number is growing," Thompson says. "So we see a great need for a preventive treatment other than surgery."
Encouraged by their years of laboratory studies, the researchers gave a one-week course of doxycycline to eight patients who were about to undergo preventive surgery for AAAs. The patients took 100 mg of the drug each morning and 100 mg each evening. After the operations, Curci analyzed aneurysm tissue that had been removed. He also looked at similar specimens from seven AAA patients who did not take doxycycline.
The results revealed that doxycycline has several potentially therapeutic
effects on aneurysm tissue in addition to its ability to inhibit the activity of
MMPs. The aneurysm samples from the patients who had not taken the
Contact: Linda Sage
Washington University School of Medicine