ABSTRACT
Fibulin-1, an extracellular matrix glycoprotein, is closely correlated with angiogenesis. The purpose of this investigation is to determine serum and vitreous fibulin-1 concentrations in diabetic retinopathy (DR). This cross-sectional investigation was carried out in a population of 154 diabetic patients (54 without DR, 42 with non-proliferative diabetic retinopathy (NPDR) and 58 with proliferative diabetic retinopathy (PDR)) and 49 control subjects. The diabetic group showed higher serum and vitreous fibulin-1 concentrations than the controls. Serum and vitreous fibulin-1 concentrations in PDR patients were significantly elevated compared with those in the other 3 groups. NPDR patients showed elevated levels of serum and vitreous fibulin-1 concentrations compared with patients without DR. Logistic regression analysis revealed that serum and vitreous fibulin-1 were risk factors for developing DR. Pearson correlation analysis showed that serum fibulin-1 was correlated with systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose and vitreous fibulin-1. Furthermore, Pearson correlation analysis showed that vitreous fibulin-1 was correlated with SBP, DBP, high-density lipoprotein cholesterol and serum fibulin-1. Serum and vitreous fibulin-1 concentrations are elevated under DR condition.
Subject(s)
Calcium-Binding Proteins/blood , Diabetic Retinopathy/blood , Vitreous Body/metabolism , Cross-Sectional Studies , Female , Humans , Logistic Models , Male , Middle AgedABSTRACT
BACKGROUND: Immune cells within a tumor microenvironment have shown modulatory effects on tumor angiogenic activity. Renal cell carcinoma (RCC) is a hypervascular tumor that reportedly increases the frequency of regulatory T cells (Tregs) in tumor tissues. This study investigated the correlation between Tregs infiltration and angiogenic status in RCC. METHODS: Thirty-six patients with RCC were enrolled in the present study, and twenty age-matched healthy donors were included as the control. Tregs were defined as CD4(+)CD25(high)CD127(low/-) T cells. The frequency of Tregs in peripheral blood and tumor infiltrating lymphocytes (TILs) were determined by flow cytometry. The expression of vascular endothelial growth factor (VEGF) in surgical resection specimens were measured with a commercial enzyme-linked immunosorbent assay (ELISA) kit. Microvessel density (MVD) was calculated on slides stained with CD34 antibody. Spearman's rank correlation was performed to evaluate the correlation between the frequencies of Tregs in TILs and VEGF values, as well as between frequencies of Tregs and MVD determinations. RESULTS: Compared to healthy controls, the frequency of peripheral blood Tregs was significantly increased in patients with RCC (P < 0.05). The percentage of tumor-infiltrating Tregs was higher than that of peripheral blood Tregs in patients with RCC (P < 0.01). In addition, the frequency of tumor-infiltrating Tregs was shown to significantly correlate with the pathological stage (P < 0.05) and nuclear grade (P < 0.01). Importantly, a significant positive correlation was observed between the frequency of tumor-infiltrating Tregs and VEGF protein expression (r = 0.51, P < 0.05), as well as between frequencies of Tregs and MVD score (r = 0.39, P < 0.05). CONCLUSIONS: These observations suggest that the high pro-angiogenic status of RCC may be associated with the accumulation of Tregs in the local microenvironment. Angiogenesis networks may be connected with immune tolerance units and cooperate with each other to facilitate tumor growth and progression.
