Association Between Macrophages with Angiogenic Cells and Microvascular Dysfunction in Astrocytic Glioma

Abstract

Objectives: Astrocytic gliomas are the most common primary brain tumours that developed from glial origin. Macrophages are the predominant inflammatory cells in infiltrating gliomas. The study aimed to investigate the association between circulating macrophages with tissue resident angiogenic cells and microvascular dysfunction in astrocytic glioma. Methods: A total of 22 astrocytic glioma patients were consented from Hospital Universiti Sains Malaysia. Tumour (n=22) were sliced and stained with CD133+ and VEGFA+ angiogenic markers and counter stained with DAPI. The Spearman rho’s test was used for the data analysis. The plasma CD68, macrophage level and von Willebrand factor level or factor VIII level (vWF/ FVIII) was measured using Elisa Kit (CUSABIO BIOTECH CO., LTD). Results: The mean plasma CD68 macrophages was 12.48±19.98 pg/ml. The mean percentage of brain tumour tissue angiogenic cells was (1.26±0.95%), adjacent normal brain tissue angiogenic cells was (0.72±0.68%). Spearman’s rho correlation test showed a significant correlation between brain tumour angiogenic cells and plasma CD68 macrophages (n=22) (Spearman’s rho, r=0.43, p=0.047). However no correlation was observed between plasma CD68 macrophages with adjacent normal brain (Spearman’s rho r =0. 019, p=0. 932). In this study vWF/FVIII level was analysed and about 14 patients with (mild factor level of >5%), 8 patients with (moderate factor level of 1-5%) and no patients had (severe factor level of <1%) was found. The mean vWF/FVIII percentage patient with mild level was 12.48±7.77 % and moderate vWF/FVIII factor level was 3.53±1.32%. The spearman’s rho correlation test showed a significant correlation between patient with moderate vWF/FVIII level with plasma CD68 macrophages (Spearman’s rho r=0.73, p=0.041). Conclusion: Circulating macrophages associated with brain tumour angiogenic cells and vWF/FVIII of astrocytic glioma. Thus targeting these parameters in the treatment of glioma might be useful. Keywords: Angiogenic cells, astrocytic glioma, brain tumour, macrophages, microvascular dysfunction