Pitfalls in the Measurement of Circulating Vascular Endothelial Growth Factor (Minireview)
Vascular endothelial growth factor (VEGF) is a specific mitogen and survival factor for endothelial cells and a key promoter of angiogenesis in physiological and pathophysiological conditions (1, 2). VEGF is required for the normal development of embryonic vasculature, the cyclic growth of blood vessels in the female reproductive tract, and the formation of capillaries during wound repair. Trials in experimental animals and human patients have shown the therapeutic potential of VEGF in coronary or peripheral arterial stenosis. However, VEGF is also involved in abnormal angiogenesis, as seen in proliferative retinopathies, rheumatoid arthritis, psoriasis, and malignancies. In fact, VEGF plays a pivotal role in tumor expansion. It locally initiates permeabilization of blood vessels, extravasation of plasma proteins, invasion of stromal cells, and sprouting of new blood vessels that supply the tumor with [O.sub.2] and nutriments and facilitate metastasis. Inhibition of angiogenesis is a novel strategy in antitumor therapy (3, 4). Initial studies revealed that the lungs, kidneys, heart, and adrenal glands are the dominant sites of expression of the VEGF gene in healthy adult animals (5). Today, it is assumed that all tissues have the potential to produce the growth factor. Its synthesis is stimulated when cells become deficient in [O.sub.2] or glucose and in inflammatory reactions. Tumor cells tend to overexpress VEGF constitutively. VEGF acts primarily in a paracrine way and binds to receptors of the basal membranes of the endothelium. Hence, the question arises as to the origin and function of blood-borne VEGF.