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(American Journal of Pathology. 2006;168:123-130.)
© 2006 American Society for Investigative Pathology

Evaluation of Angiogenesis and Vascular Endothelial Growth Factor Expression in the Bone Marrow of Patients with Aplastic Anemia

Wolfgang Füreder*, Maria-Theresa Krauth*, Wolfgang R. Sperr*, Karoline Sonneck*, Ingrid Simonitsch-Klupp{dagger}, Leonhard Müllauer{dagger}, Michael Willmann{ddagger}, Hans-Peter Horny§ and Peter Valent*

From the Department of Internal Medicine I,* Division of Hematology and Hemostaseology, the Center of Excellence for Clinical and Experimental Oncology, and the Department of Clinical Pathology,{dagger} Medical University of Vienna, Vienna, Austria; the University of Veterinary Medicine,{ddagger} Vienna, Austria; and the Department of Pathology,§ University of Lübeck, Lübeck, Germany

It is generally appreciated that bone marrow function and growth of myelopoietic cells depends on an intact microvasculature. A pivotal regulator of angiogenesis is vascular endothelial growth factor (VEGF). Here, we describe analysis of VEGF expression and microvessel density in the bone marrow of patients with aplastic anemia by immunohistochemistry. Bone marrow was examined at diagnosis and at the time of hematological remission after immunosuppressive therapy using anti-thymocyte globulin, cyclosporin A, and glucocorticoids or allogeneic stem cell transplantation. At diagnosis, both VEGF expression and microvessel density were found to be significantly lower in aplastic anemia compared to normal bone marrow (aplastic anemia, 1.1 ± 0.7 events per field, versus controls, 5.9 ± 3.0 events per field; P < 0.05). In response to successful therapy, VEGF and microvessel density in the bone marrow increased substantially. Serum VEGF levels were also found to be significantly lower at diagnosis in aplastic anemia compared to healthy controls (aplastic anemia, 51 ± 35 pg/ml versus controls, 444 ± 220 pg/ml; P < 0.05). VEGF in the serum increased substantially after successful immunosuppressive therapy or stem cell transplantation (P < 0.05). Taken together, these data show that aplastic anemia is associated with reduced angiogenesis and reduced VEGF expression.




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