Each year, 200,000 Americans find out that the largest blood vessel in their body, the aorta, may burst open at any time. About 20,000 die suddenly from such a rupture. And another 36,000 have surgery to repair or replace the swelling section of aorta before time runs out.
But despite the deadly toll of this condition, called abdominal aortic aneurysm or AAA ("triple A"), experts know very little about why it happens. Now, a pair of papers from researchers at the University of Michigan Cardiovascular Center is shedding new light on the mystery.
In the July 12 issue of the journal Circulation, U-M researchers report that a certain type of white blood cell called a neutrophil appears to be crucial to AAA formation.
Neutrophils are the "first responders" of the body's immune system, appearing rapidly on the scene of an infection or injury to an area of tissue, and sounding the alarm to summon other immune cells to join the fight. They are key to the process of inflammation by which the body fights off insults from bacteria, viruses and injuries.
The two new papers show for the first time that neutrophils are important in the very early stages of AAA formation, when the aorta wall begins to weaken and bulge. The researchers think the cells may somehow act in combination with other AAA risk factors such as smoking, high blood pressure and inherited genetic vulnerability.
The U-M researchers made the findings in laboratory experiments on mice that had been treated to wipe out their neutrophils temporarily, and in rats that lacked the protein that lets neutrophils attach to tissue and start the "first aid" process. The researchers exposed a small part of the rodent aortas to a chemical that breaks down blood vessel tissue, then studied what happened in the rodents that had altered neutrophil systems and in comparison rodents that were normal.
In both cases, says senior author and U-M vascular surgeon Gilbert Upchurch, M.D., the rodents that had low neutrophil levels or no neutrophil-attaching protein developed little or no sign of aneurysm. Meanwhile, the injury to the aorta wall prompted the rapid formation of aneurysms in the normal rodents -- aneurysms that made the diameter of the blood vessel double or even quadruple.
In an accompanying editorial, Columbia University surgeon M. David Tilson, M.D., notes that the studies bring research on AAA formation and the role of the neutrophil to a new level and may lead to further discoveries that help sort out the AAA puzzle.
AAAs are an under-appreciated and under-researched public health threat, says Upchurch, who operates on dozens of AAA patients each year, including some whose aneurysms have already burst and who will die within minutes or hours if the bleeding isn't stopped. AAAs can go undetected for years; experts sometimes refer to them as a "ticking time bomb" inside a patient's abdomen.
In fact, an estimated 10 percent of all men over the age of 70 may have intact aortic aneurysms, which cause few symptoms except for occasional back pain or abdominal discomfort. If they are detected during this stage, for instance on a routine physical exam, X-Ray, MRI or CT scan, they can be repaired successfully 95 percent of the time.
Recently, new ideas about why aneurysms form have begun to take shape. "We're finding that in general, an aneurysm is an inadequate response to injury," Upchurch explains. "Something happens to damage elastin fibers in the blood vessel wall and, for some reason, the immune system's normal healing response doesn't work. Something eats away at smooth muscle cells in the wall of the aorta until it starts to fall apart."
Researchers have found that AAAs appear to be associated with high levels of enzymes that are capable of doing that eating. But the question of how those enzymes get there, and what prompts them to arrive, has been unanswered.
"Neutrophils are known to carry some of these enzymes, called matrix metalloproteinases and chemokines, which help them attack invaders," says Upchurch. "We wanted to see what the role of neutrophils was in the early stages of aneurysm formation and the progression of the aneurysm."