TNF and atherosclerosis: A key mediator of the development of atherosclerosis is the cytokine TNF-α which, acting through its receptors on the surface of macrophage, endothelial, and smooth muscle cells of the vasculature, induces signal transduction cascades leading to NOS activity, activation of transcription factors such as Nuclear Factor kappa B (NF-κB), and production of proinflammatory adhesion molecules and cytokines such as ICAM-1, VCAM-1, and IL6.