BACKGROUND:
Receptor tyrosine kinases that include
vascular endothelial growth factor (
VEGFR)-1,
VEGFR-2, and
Tie-2 regulate
cardiovascular development and physiological and
pathological angiogenesis. We were interested in the
phenotypic and functional characterization of
peripheral blood cells expressing these receptors and their therapeutic potential in vascular
injury. METHODS AND RESULTS:
VEGFR-1+,
VEGFR-2+, and
Tie-2+ cells constituted approximately 3.0+/-0.2%, 0.8+/-0.5%, and 2.0+/-0.3%, respectively, of the total population of
mononuclear cells in
blood.
Phenotypic analysis demonstrated that all 3 cell populations mainly expressed markers of
monocytic/
macrophage lineage. Only
VEGFR-2+ and
Tie-2+ cells
phenotypically, morphologically, and functionally differentiated to
endothelial cells after culture, whereas
VEGFR-1+ cells did not. None of the cell types proliferated in vitro. Only freshly isolated
VEGFR-2+ or
Tie-2+ cells but not VEGFR-2- or Tie-2- cell populations significantly contributed to efficient endothelialization of balloon-injured
femoral arteries of
nude mice. Furthermore, these cells also differentiated into -actin-positive
smooth muscle cells. Administration of
bromodeoxyuridine to animals transplanted with human
endothelial progenitor cells showed that
VEGFR-2+ and
Tie-2+ cells proliferated in vivo. CONCLUSIONS: These data demonstrate that expression of
VEGFR-2 and/or
Tie-2 on
peripheral blood cells defines functionally competent cell populations that proliferate in vivo and that contribute to reendothelialization. These findings may have implications for a cell-based approach in vascular diseases.
