Myeloid Lineage of Human Endothelial Outgrowth Cells Circulating in Blood and Vasculogenic Endothelial-Like Cells in the Diseased Vessel Wall

Abstract

Endothelial injury is a major step in the pathogenesis of atherosclerosis. Accumulated data suggest endothelial progenitor cells can derive from various sources, including the host bone marrow, circulating blood mononuclear cells, as well as resident precursors within the vessel wall. Early experimental animal data supported a haematopoietic origin for vascular precursors, but more recently cells of myeloid lineage have been suggested as precursors of endothelial and smooth muscle cells. However, to date, little evidence exists to support a myeloid lineage-endothelial cell differentiation pathway within the vasculature of human subjects. Here, we undertook two sets of experiments aimed at determining whether (a) blood endothelial outgrowth cells (EOC) had a myeloid lineage and whether (b) chimeric endothelial-like cells within the neovasculature of gender-mismatched cardiac transplant arteriopathy subjects shared common myelomonocytic markers. We show here that in vitro blood-derived EOC and recipient-derived endothelial-like cells participating in vasculogenesis in vivo share some myeloid immunophenotypes. Additionally, these microvascular chimeric cells show no evidence of tetraploidy or cell fusion.