o Atherosclerotic Lesions Grow By Recruiting Circulating Inflammatory Cells, Which Multiply Within Arteries Atherosclerotic plaques become increasingly prone to structural failure as they gain a growing number of inflammatory cells. This structural breakdown is the cause of acute cardiovascular events such as heart attack and stroke. Through an Established Investigator Award from the American Heart Association, Dr. Galis has developed an experimental model of genetically engineered mice to study how atherosclerotic plaque forms. Through different kinds of cell surface markers, she can distinguish between circulating inflammatory cells and those already present in the arterial wall. Using this model, Dr. Galis and her colleagues, post-doctoral fellow Susan Lessner, Emory undergraduate Heather Prado and collaborator Dr. Ned Waller, have demonstrated that atherosclerotic plaques recruit circulating inflammatory cells, and that once these cells join the plaque, they multiply and contribute to the growth of the plaque. This knowledge could lead to drug-based strategies aimed at blocking the infiltration of inflammatory cells in the early stages of atherosclerotic plaque formation and blocking the proliferation of inflammatory cells in more mature plaques.
o (MMP)-9 Enzymes Enable Cells to Migrate Within Arteries and Attach to Extracellular Matrix Newly discovered functions of MMP enzymes show that they play both beneficial and harmful roles. As blood vessels and arteries develop and repair, MMPs help cells break down and reorganize or "remodel" their matrix — the complex molecular scaffold that gives arteries structural support by holding cells together. The remodeling process controlled by MMPs can be either beneficial or deleterious based on location, timing, or extent. Dr. Galis presents evidence showing that enzymes known to degrade the extracellular matrix are also essential in putting the molecules back together. For example, the same MMP-driven process of releasing the matrix barriers that initially allow an artery to enlarge in the face of a growing atherosclerotic plaque also ends up weakening the artery and creating the opportunity for a heart attack. As part of the Georgia Tech-Emory tissue engineering center funded by the National Science Foundation, Dr. Galis and graduate student Chad Johnson have discovered that MMP-9 enzymes are important in helping cells break off and migrate through the matrix proteins, and that MMP-9 enzymes with a genetic defect make it harder for these cells to migrate. They believe limiting the migration of vascular cells may be an effective therapy to limit the growth of arterial plaques that occur naturally during atherosclerosis, or during restenosis following surgical interventions aimed at widening diseased arteries.