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 failure—the 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 vessel’s structure, such as a rupture of atherosclerotic plaques.

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 collagen—the major structural protein in the body and one of the basic building blocks of blood vessels—which 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 substitutes.