Anemia and elevated systemic levels of vascular endothelial growth factor (VEGF)

Background: Tissue hypoxia is a major stimulus for the up-regulation of vascular endothelial growth factor (VEGF). Anemia might theoretically impact on angiogenesis via impairment of tissue oxygenation. We have investigated this hypothesis in patients with solid cancers and benign diseases. Patients and Methods: 49 patients with untreated locoregionally confined solid cancers of the head and neck, cervix, rectum and lung and 59 additional patients with non-malignant diseases (36 normemic patients without serious diseases and 23 patients with renal anemia) were enrolled and the impact of anemia on plasma VEGF Levels were determined. VEGF was measured with a commercially available sandwich enzyme immunoassay technique. Results: Plasma Levels of VEGF were 16.2 +/- 12.7 pg/ml in 36 normemic patients without malignant disease, 49.2 +/- 34.5 pg/ml in 49 patients with cancers (p < 0.001), and 89.9 +/- 67.8 pg/ml in 23 patients with renal anemia (p = 0.001). VEGF levels in cancer patients were significantly correlated with hemoglobin (hb) levels and platelet counts (each p = 0.001), but not with type of tumor, stage, histology or age. Patients with cancers had higher plasma levels of VEGF than patients with non-malignant diseases in case of hb greater than or equal to 12 g/dl (33.1 +/- 17.5 vs 16.6 +/- 13.0 pg/ml, p < 0.001) and in case of hb between 11.0 and 11.9 g/dl (56.1 +/- 26.4 vs 18.5 +/- 14.5 pg/ml, p = 0.038). In case of a hb <11 g/dl, plasma VEGF Levels were significantly elevated in patients with and without cancers (67.0 +/- 47.5 vs 88.9 +/- 68.8 pg/ml, n.s.). In a multivariate model, a significant association between low hb levels and increased plasma levels of VEGF was confirmed. In 16 patients with renal anemia, changes in hb under erythropoietin treatment were inversely correlated with changes in plasma VEGF Levels with decreasing VEGF after increase in hb (p = 0.01). Conclusions: Anemic patients have elevated levels of VEGF. The data suggest that anemia might impact on the progression of angiogenesis in malignant and benign diseases.