Monocytosis, Hypercholesterolemia, and the Kinase That Binds Them

Atherosclerosis is a chronic lipid-driven inflammatory disease that involves the recruitment, infiltration, differentiation, and proliferation of monocytes and monocyte-derived macrophages. In the absence of these cells, disease neither initiates nor progresses. Indeed, leukocytosis is a defining risk factor for increased cardiovascular disease in humans.1,2 Because monocytes are involved in every step of atherosclerosis disease progression,2–4 modifying anything from recruitment to proliferation could significantly affect disease severity. Any modification needs to be extremely precise, however, because the role of monocytes changes as the disease advances. Although recruitment is the underlying culprit during the initial stages,5–7 proliferation becomes consequential later.8 MAPK (mitogen-activated protein kinases), JNK (c-Jun N-terminal kinase), and NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) can have widespread effects on cell cycle and cytokine production and may therefore be promising targets in treating complex diseases. Sanz-Garcia et al9 focus on one such kinase, Map3k8, and identify how it can be targeted to alter monocyte biology and atherosclerosis.See accompanying article on page 237 Map3k8, also known as Tpl2 or Cot, …