Research may yield improved treatment for diseased lungs
ith a grant of nearly $2 million from the National
Institutes of Health National Heart Lung and Blood Institute, a multi-institutional
team of biomedical engineers, scientists and clinicians will study large-artery
biomechanics that could play a role in heart failure in patients with
pulmonary arterial hypertension.
Patients who have the disease may have narrowed, thickened
pulmonary arteries in which scar tissue accumulates, blood flow is blocked
and tiny blood clots form. There are treatments for pulmonary arterial
hypertension; however, there is no cure.
Led by Assistant Professor Naomi
Chesler, the researchers hope to create improved diagnostic tools
that enable them to track stiffening of large and small arteries and
link these measurements with impaired ventricular function.
Currently, researchers believe pulmonary arterial
hypertension is tied mostly to narrowing of the small blood vessels
that carry oxygen-poor blood from the right ventricle of the heart to
the pulmonary arteries in the lungs. “That reduction in diameter
increases resistance, and that increase in resistance overloads the
right heart, because it has to produce more pressure,” says Chesler.
But in this process, she says, researchers have downplayed
the role of stiffness in the much larger pulmonary arteries, which also
contributes to the right heart load.
For example, on the left side of the circulation,
where oxygen-rich blood from the lungs flows to the head, limbs and
major organs, researchers just recently have begun to understand that
the properties of large “conduit” arteries are important
to left-ventricle function. “Changes can occur to large vessels
that alter the way that pulse waves travel in the circulation and can
end up overloading the left ventricle—not by increasing the mean
pressure, but by altering the wave patterns,” says Chesler. “So,
a goal of this grant is to investigate whether that occurs also on the
right side. If it does, it’ll open up all sorts of new treatment
possibilities, because we haven’t been treating the large arteries
because we haven’t been thinking of them as part of the problem.”
Researchers have measured impedance, which is like
resistance but takes into account arterial stiffness, in human pulmonary
circulation since the 1960s. But while these measurements show that
large-artery stiffening occurs, the data don’t show whether that
stiffness affects ventricular function, says Chesler.
She, too, will measure impedance in the pulmonary
circulation, focusing specifically on the role of a particular protein,
collagen, in arterial stiffening. A key innovation in molecular biology
will enable Chesler to use transgenic mice to explore the physical role
of collagen-mediated large-artery stiffening in pulmonary arterial hypertension.
She will induce large-artery stiffness in the mice in a process that
mimics scleroderma, a disease in which the body produces too much collagen,
the body’s ubiquitous fibrous structural protein that strengthens
blood vessels.
On campus, Chesler’s collaborators include Cardiology
Associate Scientist Timothy Hacker, Biostatistics
and Medical Informatics Associate Scientist Jens
Eickhoff, Medicine Assistant Professors James
Runo and Nancy Sweitzer, Radiology
and Biomedical Engineering Assistant Professor Scott
Reeder, and Medical College of Wisconsin Assistant Professor
Robert Molthen.
