The VEGF family includes five members, VEGFA (VEGFA165), VEGFB, VEGFC, VEGFD, and placenta growth factor (PlGF). Structurally, these growth factors are homodimers, although VEGFA and PIGF heterodimers have been described. There are three VEGF receptor tyrosine kinases: VEGFR1 (Flt1), VEGFR2 (Flk1), and VEGFR3 (Flt4). Despite an overlapping expression of these receptors, a distribution pattern has been identified. VEGFR1 is expressed on monocytes and macrophages, VEGFR2 on vascular endothelial cells, and VEGFR3 on lymphatic endothelial cells. VEGFR2 binds to VEGFA, VEGFC, and also to proteolytically processed VEGFC and VEGFD. VEGFR2 is the major mediator of the signaling cascades that regulate endothelial cell functions, including proliferation, migration, and differentiation. Soluble VEGFR2 was initially identified in mouse and human plasma resulting from endothelial cell surface proteolytic cleavage. VEGFA stimulates ADAM17-dependent shedding of VEGFR2; also, its shedding is stimulated by phorbol ester (PMA) and the calcium ionophore, ionomycin. Soluble VEGFR1 and VEGFR2 regulate availability of VEGFA by acting as decoy receptors. In addition, alternative splicing of VEGFR2 produces a soluble VEGFR2 that binds VEGFC, which prevents lymphangiogenesis. It has been reported that a decrease in VEGFR2 plasma levels in preeclamptic women may serve as a marker of endothelial dysfunction.