These direct effects of TLR4 activation cumulatively promote bacterial translocation (76), which leads to further TLR4 activation on the endothelium, leading to loss of endothelial nitric oxide synthase (eNOS) and associated vasoconstriction (77), which in turn contributes to the development of ischemic necrosis in NEC. The gene discussed is NOS3; the disease is necrotizing enterocolitis.