Clinical application and cardiovascular adverse effects of angiogenesis inhibitors
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This thesis examines the role that angiogenesis inhibitors play in certain disease conditions and their effects on the cardiovascular system. Vascular endothelial growth factor (VEGF) is one of the most important proangiogenic growth factors, and inhibiting it directly or indirectly has led to the discovery of numerous treatment modalities. These include monoclonal antibodies, small molecule inhibitors, aptamers, gene therapy, and chimeric antigen receptor T cell therapy. They are used in the treatment of several solid tumors, melanomas, age-related macular degeneration and diabetic retinopathy, to name a few. These angiogenesis inhibitors work on angiogenic growth factors that are present in healthy and diseased conditions and have been noted to cause some side effects on the cardiovascular system. They decrease nitric oxide, increase endothelin-1 and cause capillary rarefaction, causing increased vascular resistance and vasoconstriction, which can lead to hypertension, left ventricular dysfunction, prolonged QT interval and thrombosis.