Defining the Roles of Smooth Muscle Cells and Other Extracellular Matrix Producing Cells in Late Stage Atherosclerotic Plaque Pathogenesis

• Johan BJORKEGREN, Icahn School of Medicine at Mount Sinai, New York (USA)
• Jeanette ERDMANN, Universitätsklinikum Schleswig-Holstein, Lübeck (Germany)
• Michael JONER, Deutsches Herzzentrum München (Germany)
• Nicholas LEEPER, Stanford University Medical Center, California (USA)
• Manuel MAYR, King’s College London (UK)
• Aloke FINN, CVPath Institute Inc., Gaithersburg, and University of Maryland, Baltimore, Maryland (USA)

Atherosclerotic plaque is an abnormal area within the wall of an artery resulting from damage to a specific region of the artery. Plaques grow slowly over years and have the potential to block blood flow in the artery. In an attempt to heal the injury in the artery, a variety of substances are deposited in the wall, including calcium, fat, cholesterol, cellular waste and fibrin, a material involved in blood clotting. In response to plaque buildup, cells in the artery wall multiply and secrete additional substances. This Leducq network will focus on the smooth muscle cells which line the arterial wall, and the extracellular matrix, a proteinaceous material (group of complex organic macromolecules that contain carbon, hydrogen, oxygen, nitrogen, and usually sulfur and are composed of one or more chains of amino acids)that fills the spaces between the cells and binds cells and tissues together. The TNE scientists have preliminary data showing that the arterial smooth muscle cells function in different ways in different individuals in response to the development of atherosclerotic plaque, which in turn results in a range of changes in the extracellular matrix; they believe the response of the smooth muscle cells is genetically programmed and may explain the variations in severity of atherosclerosis in humans. The investigators propose to define the various types of smooth muscle cells within human plaque and learn what determines a beneficial repairing of the artery wall or a further deterioration in the plaque quality and size. Such information could be useful in designing novel treatments for atherosclerotic disease.