Targeting blood stem cell activity and extramedullary monocytopoiesis to treat atherosclerosis
Final Report Abstract
Myocardial infarction increases splenic myelopoiesis and production of inflammatory monocytes that aggravate atherosclerotic plaque inflammation. In an atherosclerotic mouse model, we show that inhibition of the adhesion molecule E-selectin reduces proliferation of hematopoietic stem and progenitor cells in the spleen after myocardial infarction. The decreased proliferation of progenitor cells led to diminished splenic myelopoiesis and reduced levels of circulating leukocytes. This was accompanied by decreased atherosclerotic plaque size in the aortic sinus. Further, atherosclerotic lesions after E-selectin inhibition were more stable, as necrotic core diameters decreased and fibrous cap thickness increased. In summary, inhibition of E-selectin is a promising target to curb splenic myelopoiesis in atherosclerotic conditions after myocardial infarction.
