Abstract 340: Novel Molecular Mechanisms Involved In VEGFR Inhibition In Human Endothelial Cells

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 2014-09, Vol.64 (suppl_1)
• Main Author: SMALL, HEATHER Y
• Format: Article
• Language: English
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/hyp.64.suppl_1.340

Abstract only VEGF/VEGFR inhibitors are increasingly being used as anti-angiogenic drugs to treat cancer. However these drugs are limited by the development of severe hypertension. Molecular mechanisms whereby VEGF inhibitors cause hypertension are unclear, but nitric oxide (NO) signalling may be involved. We questioned whether reactive oxygen species (ROS) and Ang II, important regulators of vascular function in hypertension, also play a role in VEGF inhibitor-induced vascular dysfunction. Human microvascular endothelial cells (HMECs) were stimulated with vatalanib (VAT-VEGFR inhibitor) and gefitinib (GEF-EGFR inhibitor) in the absence/presence of Ang II. Activation of eNOS and MAPKs were assessed by immunoblotting. Antioxidant enzyme mRNA was analyzed by qPCR. Phosphorylation of eNOS activation site (Ser1177) (28.3% ± 7.1) and p38 MAPK (55.4% ± 2.4) was decreased by VAT, while no changes were observed after exposure of HMECs to GEF (p