VEGF inhibition is known to increase mitochondrial superoxide generation and decrease nitric oxide (NO) production.47 This results in the acceleration of atherosclerosis in apolipoprotein E (apo E) knockout mice with no discernible effects on plaque vulnerability.26 Experiments in rats treated with sunitinib demonstrated reduced vasorelaxation due to a reduction in endothelial NO release.48 Small molecule TKIs such as ponatinib and nilotinib are associated with increased incidence of myocardial ischemia or infarction.49 Ponatinib is also associated with an increased risk of angina pectoris. This evidence concerns the gene APOE and myocardial ischemia.