Bone marrow angiogenesis in patients presenting with differential Chinese medicine syndrome: Correlation with the clinico-pathological features of aplastic anemia

To explore differences in bone marrow angiogenesis seen in aplastic anemia (AA) patients presenting with differential Chinese medicine (CM) syndrome, and to correlate these differences with clinical pathology. Thirty-five patients were enrolled, including 18 with yang deficiency syndrome and 17 with yin deficiency syndrome. Bone marrow biopsies and serum were collected. Microvessel density (MVD) and positive expression of vascular endothelial-derived growth factor (VEGF) were detected by immunohistochemisty. Hypoxia inducible factor -1 alpha (HIF-1 alpha), and VEGF expression were assayed by enzyme-linked immunoabsorbent assay (ELISA), serum lactate dehydrogenase (LDH) was tested by enzyme method and liquid chip technology was used to detected the expression of interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha. Counts for leukocytes, absolute neutrophils and platelets in yin deficiency syndrome were lower than those found in yang deficiency syndrome (P < 0.05). MVD and VEGF expression, and the positive rate of CD34 and VEGF in bone marrow were lower in AA, especially in yin deficiency syndrome (P < 0.01 or P < 0.05). Yin deficiency syndrome displayed decreased VEGF and LDH expression, and enhanced expression of HIF-1 alpha as compared to yang deficiency syndrome (P < 0.05). Levels of IL-4 and IL-6 were higher in AA (P < 0.01), but IL-10 was decreased (P < 0.05). High TNF-alpha expression was seen in yang deficiency syndrome and IFN-gamma expression was decreased in yin deficiency syndrome as compared with normals (P < 0.01 and P < 0.05, respectively). AA patients have lower MVD than normals, especially in yin deficiency syndrome. MVD might differentially correlate to disease severity, and could be dependent on bone marrow or serum VEGF expression and LDH. Additionally, IL-2, IL-10, IL-4 and IFN-gamma were negatively associated while IL-6 and TNF-alpha were positively associated with MVD.