A quarter of all deaths in Canada are caused by complications associated with cardiovascular disease. The main cause of vascular disease is atherosclerosis, or build-up of plaque in the arteries. Atherosclerosis is an inflammatory disease. One subset of inflammatory cells, macrophages, play an important role in atherosclerosis progression. How these cells gather in plaques, however, is not clear. Macrophages can appear in plaques through recruitment of their monocyte precursors from the bloodstream. Our recently published data shows macrophages also proliferate or divide locally within the plaque. We are currently pursuing three main research streams:
- Investigating the role of lesional macrophage proliferation in atherosclerosis.Which process - monocyte influx or macrophage proliferation - is more important? What are the mechanisms that drive proliferation? How does the balance between the two processes change with co-morbidities and treatment? Does one process influence the other? Which of the two is the better therapeutic target? The answers to these question are likely to identify new therapeutic targets in treating atherosclerosis.
- Determining the contribution of embryonic- versus bone marrow-derived macrophages in atherosclerosis.Some macrophages develop from hematopoietic stem cells, while others develop prior to birth and independent of the bone marrow. We ask the important question whether functional differences exist between these different macrophage populations and to what extent each population contributes to disease.
- Determining the molecular mechanisms that regulate macrophage accumulation in atherosclerosis.In addition to growth factors, hematopoiesis is tightly controlled at the transcriptional level. One such transcription factor, c-Myb, has been demonstrated to play an important role in the survival, proliferation, and differentiation of hematopoietic cells. We are currently studying the role of c-Myb in regulating inflammation in atherosclerosis.
Senior Scientist, Toronto General Hospital Research Institute (TGHRI)
Professor, Department of Laboratory Medicine and Pathobiology, University of Toronto