OxLDL Inhibits Brain Angiogenesis in Dose Dependent Manner via Reducing Level of VEGF and Angiopoietin-2: A Comprehensive Study

Hyperlipidemia is recognized as a major health problem worldwide, moreover, it is considered as a major risk factor for cardiovascular and cerebrovascular diseases development. Since the majority of studies were performed to investigate the effect of hyperlipidemia on the angiogenesis of peripheral derived endothelial cell, this study aims to assess the effect of hyperlipidemia on the angiogenic response of human brain cells in a fast, easy and inexpensive method. Furthermore, it aims also to assess the involvement of Vascular Endothelial Growth Factor (VEGF) and angiopoietin. To achieve this aim, human Brain Microvascular Endothelial Cells (hBMECs) were treated with different concentration of Oxidized Low Density Lipoprotein (OxLDL) (1-100 μg/ml) for 24 hours. Migration rate and tube formation as markers of angiogenesis were performed, also Coomassie blue was used to detect protein level. OxLDL was found to inhibit brain angiogenesis in dose dependent manner over a wide range of concentrations (1-100 μg/ml). Using 1 μg/ml of OxLDL made minimum reduction of 10% whereas using 100 μg/ml of OxLDL resulted 70-80% reduction in the angiogenic potential of hBMECs within 24 hours. Moreover, OxLDL mediated its effect through reduced VEGF level and this effect was partially reversed by administered 5 ng/ml of VEGF. Additionally, OxLDL reduced the level of angiopoitin-2. This further supports the assumption that OxLDL has an anti-angiogenic effect in hBMECs and surely in the brain also. As a conclusion, OxLDL inhibits brain angiogenesis in dose dependent manner through reducing the level of angiogenic factor in human brain microvascular endothelial cells. We achieved our goal of having a preliminary indicator of brain angiogenesis under hyperlipidemia by using a simple but well-developed technique that incorporated the minimal number of tests and the cheapest.