A team of researchers at the University of Nebraska Medical Center has
identified an enzyme potentially involved in the growth of aortic aneurysms
a silent condition that, when ruptured, claims the lives of 15,000 Americans
each year.
The discovery, reported in the October issue of Arteriosclerosis, Thrombosis
and Vascular Biology the Journal of the American Heart Association, could
lead to future lifesaving treatment options that dont require surgery.
About 2 percent of the population is affected by aortic aneurysms,
said Timothy Baxter, M.D., associate professor of surgery at UNMC and the
studys principal investigator. In Nebraska, thats about 25,000 people
many of whom dont know they have the condition.
The aorta is the main trunk of the bodys arterial system. It carries
blood from the heart to each of the branch arteries for distribution throughout
the body. When an aortic aneurysm occurs, the aorta starts to expand in
a localized area. If it expands too much, the aorta eventually can rupture,
resulting in death in many instances.
About 95 percent of aneurysms occur in the abdomen where the aorta branches
off to supply blood to each leg. There usually are no warning signs of
an aortic aneurysm, Dr. Baxter said. It usually is detected by an abdominal
X-ray or when a physician feels the aneurysm in a persons abdomen.
Dr. Baxter and his research team identified the enzyme, known as matrix
metalloproteinase-2, by studying tissue from abdominal aortic aneurysms
(AAA) and comparing it with tissue from other known vascular disease conditions.
High amounts of the enzyme were found in the AAA tissue, but not in the
comparison tissue samples.
Now that the enzyme has been identified, the research team will seek
ways to block its growth through drug intervention. We are able to block
this enzyme in cells grown in culture, but there are many examples of drugs
effective in the laboratory which have not worked in clinical trials,
Dr. Baxter said. This will have to be studied very carefully as we move
to patient trials.
A series of clinical trials will begin next month on campus to test
the effectiveness of a tetracycline derivative in blocking the enzyme and
stopping the growth of the aneurysm. Dr. Baxter said he hopes to enroll
30 patients in the pilot study.
Currently, surgery is the only proven treatment option available for
patients with aortic aneurysms. If detected early enough, repair of the
aortic aneurysm can eliminate this silent danger. In 1996, Dr. Baxter and
a team of surgeons from UNMC performed the first ever laparoscopic surgical
repair of an aortic aneurysm.
Surgery, however, is only an option for aortic aneurysms that have grown
to a certain size, Dr. Baxter said. Small aneurysms if detected are
not treated, but are monitored over time for growth.
Ultrasound is an effective way to detect aortic aneurysms. It isnt
cost-effective today, though, because we dont treat aneurysms when they
are small, Dr. Baxter said. If we could identify a drug that could halt
the growth of aortic aneurysms, we could effectively treat the condition
when the aneurysm is small long before it has a chance to rupture.
If early drug intervention becomes standard therapy, he noted, screening
for aortic aneurysms could become as commonplace as screenings for breast,
prostate and colon cancer.
Although the exact cause of aortic aneurysms is not known, factors that
contribute to the weakening of the artery wall are:
–High blood pressure.
–Smoking.
–Male gender.
–Age (55 and older).
–A family history of aortic aneurysms.
Men are nearly four times as likely as women to have an aneurysm, Dr.
Baxter said, but noted that aneurysms are increasing in women. The average
age of patients who have aneurysms is 70. Many of these patients are smokers
or ex-smokers, he noted.
For more information about the study or the coming clinical trials
at UNMC, contact Dr. Baxter at (402) 559-4395.
UNMC is the only public academic health science center in the state.
Through its commitment to research, education and patient care, UNMC has
established itself as one of the countrys leading centers for cancer research
and treatment and solid organ transplantation. More than $34 million in
research grants and contracts are awarded to UNMC scientists annually.
In addition, UNMCs educational programs are responsible for training more
health professionals practicing in Nebraska than any other institution.