April 2, 2001
Galis simplifies the matrix of cardiovascular health
By Holly Korschun
Cardiologist Zorina Galis has made significant discoveries about a class
of enzymes called matrix metalloproteinases (MMPs) and the important role
they play in cardiovascular health and disease.
Galis pioneered the notion that blood vessels rely on MMPs for development and repair, but excessive weakening of the arteries by these enzymes can lead to structural failurethe cause of acute cardiovascular events such as heart attack and stroke.
A member of the Department of Medicine (cardiology) and the Emory-Georgia
Tech Department of Biomedical Engineering, Galis studies the normal and
pathological reshaping of blood vessels. During this remodeling
process, blood vessels, with the help of MMPs, break down and reorganize
their extracellular matrix, the complex molecular scaffolding that holds
cells together within a tissue.
Although MMPs are necessary for development and repair of blood vessels,
when degradation of the scaffold is inappropriate or carried too far,
these same enzymes can cause serious, even life-threatening damage to
the blood vessels structure, such as a rupture of atherosclerotic
These plaques contain cholesterol and lipids and build up during the
life of an artery; rupture causes artery blockage, which triggers heart
attacks and strokes.
Control of the degrading action of MMPs should improve the strength of
atherosclerotic arteries and thus decrease the number of clinical cardiovascular
events, including death.
Galis is applying knowledge about MMPs and matrix remodeling obtained
from native blood vessels to tissue engineering for the development of
substitute blood vessels that mimic native arteries. These tissue-engineered
vessels could be used to replace diseased arteries and would be particularly
useful in coronary artery bypass surgery.
To construct an artificial vessel, Galis and her colleagues in the Georgia
Tech-Emory Center for the Engineering of Living Tissues use collagenthe
major structural protein in the body and one of the basic building blocks
of blood vesselswhich they seed with vascular cells.
They then mechanically precondition these vessels to enhance the reorganization
of the engineered tissue and improve its mechanical properties.
Galis has shown that cells use MMPs in this process, as MMP inhibition
impairs organization of the collagen scaffold. However, as within native
blood vessels, excessive MMP activity weakens the vascular tissue constructs.
Galis said she believes her research is helping scientists understand
the delicate balance between the beneficial and deleterious effects of
MMPs on blood vessels, which should lead to improvements in the treatment
of atherosclerotic plaques as well as the development of improved tissue