Cardiovascular disease is the leading cause of death in developed countries. Inflammation aggravates outcome of cardiovascular disease including atherosclerosis and infarct healing after myocardial infarction (MI). During progression of atherosclerosis, myeloid cells destabilize lipid-rich plaques in the arterial wall and cause their rupture, thus triggering myocardial infarction and stroke. Survivors of acute coronary syndromes have a high risk of recurrent events for unknown reasons.
Another area of my research interest is fate and differentiation of hematopoietic stem and progenitor cells in cardiovascular disease. Hematopoietic stem cells get activated after acute or chronic inflammation and give rise to exaggerated myelopoiesis. However, most hematopoietic stem cells (HSC) are quiescent, and it is currently unknown whether they respond to ischemic organ injury. We identified a CCR2+ HSC subset, which has fourfold higher proliferative rate than CCR2- HSC, as the most upstream contributor to myelopoiesis after myocardial infarction. CCR2+ HSC display bias towards the myeloid lineage and dominate the migratory HSC population after myocardial infarction and in steady-state. These data shed new light on the regulation of emergency hematopoiesis after ischemic injury and identify novel therapeutic targets to modulate leukocyte output after myocardial infarction.